Skin Architecture, ECM, and Cellular Components: History
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Contributor:
Erna Raja
,
Maria Thea Rane Dela Cruz Clarin
,
Hiromi Yanagisawa

Matricellular proteins are nonstructural, modular, extracellular proteins that exert their effects by binding to cell surface receptors, extracellular matrix (ECM) proteins, soluble signaling molecules, and proteases, thereby modulating cellular responses to changes in their microenvironment, particularly during tissue remodeling. The skin is the largest organ of the body and protects us against environmental insults. It shields the body from mechanical abrasion, pathological infections, dehydration, and fluctuations in body temperature, while the nerves in the skin also provide us with sensations of touch. The skin needs to act as a resilient mechanical barrier, yet provide structural flexibility. The functional unit of skin consists of the stratified epidermis and dermis (including dermal adipose and skin appendages such as hair follicles, sweat, and sebaceous glands) as well as the panniculus carnosus (PC) muscle and the subcutaneous fascia. Notably, the human skin has a thicker epidermis and dermis compared with mouse skin, and the epidermis exhibits undulations forming the rete ridge and inter-ridge (also known as dermal papillae) structures that are absent in mouse skin.

  • matricellular proteins
  • basement membrane
  • extracellular matrix
  • epidermal stem cells

1. Epidermis

The construction of the epidermis begins with the basal epidermal stem cells that undergo a continuous and balanced process of symmetric self-renewal and asymmetric division to produce progenitors and differentiated cells. These provide a constant supply of keratinocytes committed to terminal differentiation which form the suprabasal layers and the cornified skin barrier [1]. Through hemidesmosomes and integrin receptors, the basal epidermal stem cells are anchored to the basement membrane (BM), which connects the epidermis to the underlying dermis. The BM’s primary constituents are structural scaffolding matrix proteins such as collagens IV, VII, XVII, laminin 332, and laminin 511 [2]. Fibronectin is also present in the lamina lucida of the BM (the laminin-rich area) [3]. Matricellular proteins, such as fibulin 2 [4][5], fibulin 7 [6], SPARC [7][8], hemicentin 1 (fibulin 6) [9][10], THBS1 [11], and thrombospondin 5 (THBS5 or COMP) [12], are contained in the epidermal BM via interactions with structural proteins or the integrin receptors.
Functionally, fibulin 2 binds to laminin 332 to stabilize the epidermal BM in neonatal skin. The absence of fibulin 2 results in separation of the dermal–epidermal junction (DEJ) and skin blisters [4]. Fibulin 7 is also expressed in the epidermal BM and has been shown to bind to collagen IV in vitro [6], although its role in the BM arrangement remains unknown. SPARC was similarly shown to bind to collagen IV in vitro and induce collagen IV and VII expression in the epidermal BM in reconstructed human three-dimensional skin culture models [7][8][13]. Hemicentin 1 co-localizes with laminin α2 at the epidermal BM [9]. Hmcn1 null mice exhibit unevenly widened lamina lucida and lamina densa and compromised hemidesmosomes [9], which suggests its function in BM organization. Hemicentin 1 was further shown to compete with laminins for its binding site to the nidogen 2 proteoglycan during BM formation and maintenance [10]. In contrast to other matricellular proteins in the BM, THBS1 is believed to act as an endogenous angiogenesis inhibitor, forming a barrier between the nonvascular epidermis and the vascularized dermis [14][15]. Matricellular proteins at the BM/DEJ, such as fibulin 2 and SPARC, are produced by both keratinocytes and fibroblasts [4][16][17][18][19], with hemicentin 1 and COMP mainly being secreted by fibroblasts [9][20]. In contrast, a subset of basal keratinocytes expresses Thbs1, albeit at low abundance during homeostasis [21]
In addition to keratinocytes, the epidermis is home to resident immune cells and melanocytes, which provide pigmentation to the skin and hair [22]. Melanocytes are regenerated by melanocyte stem cells, which are neural-crest-derived cells. Melanocytes produce melanin and have long dendrites that can make physical connections with up to 40 keratinocytes. Melanin is transferred to keratinocytes via caveolae-dependent internalization (lipid-raft-mediated endocytosis) to protect their nuclei from ultraviolet (UV) radiation [23]. Melanocyte survival also depends on its attachment to the epidermal BM via binding between its discoidin domain receptor 1 (DDR1) and collagen IV [24]. During stress or UV radiation, keratinocytes secrete paracrine factors such as IL-1β that, in turn, induce melanocytes to secrete the matricellular protein CCN3. CCN3 promotes DDR1 binding to collagen IV and inhibits melanocyte proliferation [24][25].

2. Dermis

Underneath the epidermal BM are the papillary and reticular dermal compartments, which are distinct in their cellularization and ECM components (Figure 1) [26]. The upper dermis/papillary dermis is densely populated with papillary fibroblasts that reside within thin and loose networks of fibrillar collagens (I and III) and elastic fibers. They produce ECMs such as collagen VI [27], fibronectin, and the matricellular proteins tenascin C and fibulin 2 [16]. These ECM proteins interact with each other to maintain structural integrity and provide biological cues for the surrounding cells. Fibronectin is a glycoprotein required for the formation of microfibrils. It acts as a scaffold for the elastic fibers, modulates the balance of skin rigidity and elasticity, and supports cell attachment and migration along the ECM matrix, such as collagen fibers [28][29]. Fibronectin also possesses growth-factor-binding ability [30][31]. Collagen VI fibrils interact with both fibronectin and collagen I [32] and may promote the tensile strength of the skin [33]. While fibulin 2 binds to fibrillin 1 and regulates the homeostasis of elastic fibers [34][35], further maintenance of the dermal ECM may come from the binding of tenascin C to fibronectin, collagen, and periostin [36]. Tenascin C has been reported to control cell proliferation by acting as a constitutive ligand to activate the cell surface epidermal growth factor receptor [37][38] and by sequestration of soluble growth factors such as Wnt3a, TGFβ, and VEGF [36][39][40][41]. Similarly, periostin is expressed in the papillary dermis, interacts with fibronectin, collagen I, and tenascin C [42] and is reported to modulate collagen structure and stability [43]. Periostin also impacts keratinocyte proliferation via fibroblast paracrine secretion of IL-6 [44].
Figure 1. Schematic presentation of mouse and human dorsal skin. Abbreviations: DP, dermal papilla; DS, dermal sheath; pc, panniculus carnosus muscle; s.c. fat, subcutaneous fat; APM, arrector pili muscle; GAGs, glycosaminoglycans. The sweat gland is not shown in the image. Matricellular protein constituents and their roles are summarized in Table 1. Created with BioRender.com (accessed on 13 February 2023).
Table 1. Matricellular proteins in different compartments of the skin.
Skin
Compartment		 Matricellular
Protein		 Function References & Study Model
Epidermis Fibulin 2 binds to laminin 332 for BM Stability [4] (mouse)
Fibulin 7 BM localization, binds to collagen IV in vitro [6] (mouse)
SPARC binds to collagen IV in vitro and induces expression of collagen IV and VII [7] (human skin & 3D culture), [8] (molecular structure), [13] (summary of works in mouse)
Hemicentin 1
(Fibulin 6)		 BM stability [9] (mouse), [10] (mouse & zebrafish)
Thrombospondin 1 inhibits angiogenesis [11] (human skin), [14] (summary of works in mouse), [15] (mouse xenograft)
CCN3 promotes DDR1 binding to collagen IV and inhibits melanocytes proliferation in UV-mediated stress [24] (human skin reconstructs), [25] (summary of works in human skin & cell culture)
Dermis Tenascin C growth factors sequestration,
regulates cell proliferation		 [36] (summary), [37] (mouse NR6 cells), [38] (human skin), [39] (mouse), [40][41] (molecular interactions)
Fibronectin * growth factor sequestration,
supports cell attachment and migration		 [30] (summary), [31] (mouse)
Fibrillin 1 * supports elastic fiber formation and homeostasis [34] (human & bovine tissue)
Fibulin 2 [35] (mouse), [34] (human & bovine tissue)
[45] (summary in human & mouse), [46][47] (human genetic mutations), [48] (mouse)
Fibulin 4
Fibulin 5
Periostin modulates collagen structure and stability, regulates keratinocyte proliferation [43] (human skin), [44] (mouse skin 3D culture)
Thrombospondin 1 dermal vascularization balance,
interacts with collagen I		 [14] (summary), [15] (mouse xenograft), [49] (in vivo mouse & human dermal fibroblasts)
Thrombospondin 2 collagen structural arrangement and abundance [50] (mouse)
SPARC [51] (mouse)
Dermal adipose tissue SPARC wound healing, modulates adipogenesis [52][53] (mouse)
CCDC80/URB/DRO1 modulates adipogenesis [54] (mouse tissue and 3T3-L1 cells), [55] (human & mouse tissue), [56] (mouse)
Hair follicle Fibulin 1 BM homeostasis [57] (mouse), [58] [summary]
Periostin tendon-related genes, may provide stability for arrector pili muscle and hair follicle connection [58][59] (mouse), [60][61] (rat)
Tenascin C
SPARC
Sebaceous glands Fibronectin* regulates cell differentiation [62] (mouse)
Tenascin C growth factor sequestration [63] (human & mouse eyelids)
Panniculus
carnosus muscle		 Fibulin 4 Panniculus carnosus muscle homeostasis [64] (mouse)
* Fibrillin 1 and Fibronectin are not classified as matricellular proteins, but they bear non-structural functions too via binding to matricellular proteins or regulating growth factors bio-availability.
The softer papillary dermis serves as a cushion connecting the stiffer epidermal BM to the lower reticular dermis, a major part of the dermal compartment. Reticular dermis contains more sparsely distributed reticular fibroblasts, thick and highly organized collagen bundles that contribute to skin tensile strength [2][26]. Reticular fibroblasts produce ECMs such as collagen I, fibrillin 1, fibronectin, emilin 1, and the matricellular proteins THBS1, tenascin C, and fibulin 2 [16]. Fibrillin 1, elastin, emilin 1, fibronectin, and matricellular proteins such as fibulin 2, 4, and 5 are expressed in the dermis and crucial for the formation of elastic fibers, which provide the skin with elastic properties [45][46][47][48][65]. Aside from regulating the balance of dermal vascularization, THBS1 is physically associated with the collagen I KGHR motif, which is important for cross-linking. The loss of this interaction results in abnormal collagen I and human dermal fibroblast differentiation into myofibroblasts [49]. Similarly, Thbs2 knockout mice have disarranged collagen fibril sizes and patterns in the dermis, which correlate with reduced skin tensile strength [50]. Abnormal collagen fibrils have also been observed in SPARC null mice, which exhibit decreases in the amount of dermal collagen I, the fibril diameter, and the tensile strength [51].
Fibroblasts in the embryonic/neonatal mouse skin are proliferative. However, in the mature skin, fibroblasts cease to divide and produce more ECM in the dermis. This ECM (collagen) enrichment in the adult skin acts as negative feedback to further inhibit fibroblast proliferation, although this quiescent state is reversible and fibroblasts are activated again upon skin injury [66]. Resident dermal immune cells are also activated to produce various cytokines that modulate fibroblast differentiation and proliferation [66][67]. Dermal fibroblasts originate from a common multipotent mesenchymal cell progenitor (expressing Pdgfrα, Dlk1, and Lrig1) that give rise to papillary and reticular fibroblast progenitors [67].

3. Dermal Adipose Tissue

Reticular fibroblast progenitors can give rise to adipocyte precursors and mature, lipid-filled adipocytes [67][68], which constitute the dermal fat layer. Dermal adipose functions as energy storage, thermal insulation, and mechanical support. Furthermore, it harbors innate immune antimicrobial functions [69][70]. Mature adipocytes express the collagen IV BM protein, which is deposited pericellularly and is believed to act as a strong scaffold to protect cells from mechanical stress in this loose connective tissue [71][72]. Collagen IV expression around these adipocytes is increased in obese compared with lean human subcutaneous adipose tissue [73], possibly to counterbalance the physical changes associated with an increase in adipocyte cell size. Other ECMs associated with skin adipose are collagen I, III, V [74], and VI [75]. Proteoglycans such as versican, biglycan, and decorin are also expressed in adipose tissue in order to bind to collagens, support their scaffolding function, and counteract compressive forces. However, in cases of obesity, these proteoglycans are present in excessive amounts, resulting in ECM defects and the promotion of tissue inflammation [76][77][78]. Adipogenesis is influenced by the matricellular protein SPARC, as its loss of expression leads to increased dermal adipose tissue [52] and accelerated wound healing [53]. Similarly, the secreted protein coiled-coil domain containing 80 (CCDC80/URB/DRO1) is highly expressed by adipocytes to modulate adipogenesis, and its genetic deletion in mice promotes body fat deposition, including subcutaneous fat [54][55][56].

4. The Hair Follicle

The hair follicle structure spans from the hypodermis (dermal adipose) up to the epidermis. Its size changes according to the hair cycle, which consists of the telogen (resting), anagen (growing), and catagen (regression) phases [79]. Hair follicles are connected to the sebaceous glands, arrector pili muscles, and dermal papilla at the base of the follicle (Figure 1 and Figure 2). During homeostasis, the hair follicle is mainly regenerated from hair follicle stem cells in the bulge region, with coordination from signals originating from mesenchymal cells in the dermal papilla, which control the exit from telogen and the duration of anagen [80][81][82][83][84][85] (Figure 2). The dermal papilla cells are, in turn, replenished by a subset of dermal sheath cells, which have self-renewal ability, also referred to as hair follicle dermal stem cells [81]. Hair follicle BM proteins are expressed by both epithelial cells and fibroblasts, with distinct contributions [86]. They consist of core structural BM proteins such as laminins, collagens IV, VI, VII, XVII, and XVIII, netrins 1 and 4, fibronectin, nephronectin, and matricellular proteins such as periostin, tenascin C, fibulin 1, SPARC, SMOC1, spondin-1, and R-spondin 3 [28][86][87]. The function of fibulin 1 is likely related to the regulation of BM homeostasis through its binding to laminin and collagen IV [57][88]. Nephronectin is produced by hair follicle stem cells to form an adhesion point for the arrector pili muscle cells expressing α8β1 integrins. Arrector pili muscles and the sympathetic nervous system cooperate with hair follicles to achieve piloerections to keep warm air closer to the skin in response to cold temperatures or emotions [58]. It has been proposed that hair follicle stem cells expressing periostin, tenascin C, and SPARC resemble tendon-related gene functions, i.e., they are expressed in the tendonous part of muscle tissue, which strengthens the bone–muscle connection and allows for skeletal movement [59][60][61]. Similarly, their deposition in the hair bulge matrix may stabilize the connection between arrector pili muscles and hair follicles during piloerections [58].
Figure 2. The hair follicle in anagen (growth phase, left) and telogen (resting phase, right) and the associated matricellular proteins in the hair follicle stem cell niche (bulge region, green box) and dermal papilla niche (yellow box). Adapted from BioRender.com (accessed on 2 August 2023).

5. The Sebaceous Gland

Sebaceous glands are located in the upper and permanent area of the hair follicle (junctional zone) in hair-associated skin. However, they may also be present in the skin independently of hair follicles such as in the meibomian glands of the eyelid [89][90]. The peripheral (basal) epidermal cells of these glands are proliferative and contain sebaceous gland stem cells. The differentiated sebocytes reside in the inner layer of the gland. Through cell death and lysis, lipids/sebum are released onto the skin surface to promote barrier functions, water repulsion, and antimicrobial- and antioxidant activities (vitamin E) [90][91][92]. Documentation regarding the ECM of the sebaceous gland is limited. A recent report indicated expression and interaction of fibronectin with the sebaceous gland basal cells to regulate its differentiation [62]. Another report discussed the ECM in the meibomian glands such as collagen IV, laminin α2, and β1, which may serve as BM scaffolding proteins, and the matricellular protein tenascin C, which may modulate growth factor bioavailability around sebaceous gland stem cells [63].
Table 2. Matricellular proteins for maintenance of hair follicles and sebaceous gland stem cells.
Process Matricellular
Protein		 Function References & Study Model
Hair follicle stem cells homeostasis Tenascin C promotes WNT signaling and maintains hair follicle stem cells [39] (mouse)
Periostin pro-cell proliferation in the hair follicles post-wounding [93] (mouse)
CCN2 maintenance of hair follicle stem cell quiescence [94] (mouse)
R-spondin 2 activates hair follicle stem cells, cell proliferation of dermal papilla and dermal sheath [95] (human hair follicles & mouse), [96] (human scalp & mouse skin, [81] (mouse)
R-spondin 3 cell proliferation of dermal papilla and dermal sheath [81] (mouse), [96] (human scalp & mouse skin)
Mindin (Spon2) gene expression is decreased in aging hair follicle stem cells, role unknown in the hair follicle [97] (mouse)
Thrombospondin 1 gene expression is increased in aging hair follicle stem cells, hair follicle and vasculature regression in catagen [97] (mouse skin), [98] (mouse)
Sebaceous gland stem cells Fibronectin * maintenance of basal sebocytes [62] (mouse)
* Fibronectin is not classified as matricellular proteins but they bear non-structural functions too via binding to matricellular proteins or regulating growth factors’ bio-availability.

6. The Panniculus Carnosus Muscle

The PC muscle is a layer of skeletal muscle located directly under the dermal adipose tissue in some mammals to facilitate skin movement independently of deeper muscle mass. The PC muscle has been suggested to mediate skin twitching during irritation, facial skin movement for social expressions, shivering thermogenesis, and skin contraction to promote wound closure [99]. In humans, PC muscle remnants exist only in certain anatomical regions, such as the craniofacial muscle, the platysma muscle (ventral region of the neck), and the palmaris brevis in the hand [99]. The PC muscle is reported to be highly regenerative [100] and vascularized [101]. The fibulin 4 matricellular protein may regulate PC muscle homeostasis, as the Fbln4 E57K homozygous mutation (the equivalent of the human mutation causing cutis laxa) in mice exhibits a thinner dermis and PC muscle layer, possibly due to elastic fiber defects and abnormal collagen fibrils [64]. However, it is unknown whether this mutation compromises PC muscle function.

7. Subcutaneous Fascia

The subcutaneous fascia ECM is enriched in an aqueous matrix containing glycosaminoglycans such as hyaluronan to facilitate smooth gliding between the skin and muscle. Fibroblasts and fasciacytes contribute to ECM production in the fascia [102]. Fibroblasts secrete fibrous matrix components such as fibrillin, elastin, fibronectin, and collagens I and III, whereas hyaluronan is produced by fasciacytes [103]. Fasciacytes are round, fibroblast-like cells expressing vimentin [104]. Little is known about the role of matricellular proteins in subcutaneous fascia maintenance, although the loss of fibulin 3 compromises elastic fibers in the visceral fascia [105][106]. Interestingly, lineage tracing experiments have demonstrated that, during wound healing, fascia fibroblasts are mainly responsible for generating scar tissue and not dermal fibroblasts [107][108].

This entry is adapted from the peer-reviewed paper 10.3390/ijms241814274

References

  1. Lippens, S.; Denecker, G.; Ovaere, P.; Vandenabeele, P.; Declercq, W. Death penalty for keratinocytes: Apoptosis versus cornification. Cell Death Differ. 2005, 12 (Suppl. 2), 1497–1508.
  2. Nystrom, A.; Bruckner-Tuderman, L. Matrix molecules and skin biology. Semin. Cell Dev. Biol. 2019, 89, 136–146.
  3. Fleischmajer, R.; Timpl, R. Ultrastructural localization of fibronectin to different anatomic structures of human skin. J. Histochem. Cytochem. 1984, 32, 315–321.
  4. Longmate, W.M.; Monichan, R.; Chu, M.L.; Tsuda, T.; Mahoney, M.G.; DiPersio, C.M. Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin alpha3beta1 in the epidermis. J. Investig. Dermatol. 2014, 134, 1609–1617.
  5. Utani, A.; Nomizu, M.; Yamada, Y. Fibulin-2 binds to the short arms of laminin-5 and laminin-1 via conserved amino acid sequences. J. Biol. Chem. 1997, 272, 2814–2820.
  6. Raja, E.; Changarathil, G.; Oinam, L.; Tsunezumi, J.; Ngo, Y.X.; Ishii, R.; Sasaki, T.; Imanaka-Yoshida, K.; Yanagisawa, H.; Sada, A. The extracellular matrix fibulin 7 maintains epidermal stem cell heterogeneity during skin aging. EMBO Rep. 2022, 23, e55478.
  7. Nakamura, T.; Yoshida, H.; Ota, Y.; Endo, Y.; Sayo, T.; Hanai, U.; Imagawa, K.; Sasaki, M.; Takahashi, Y. SPARC promotes production of type IV and VII collagen and their skin basement membrane accumulation. J. Dermatol. Sci. 2022, 107, 109–112.
  8. Sasaki, T.; Hohenester, E.; Gohring, W.; Timpl, R. Crystal structure and mapping by site-directed mutagenesis of the collagen-binding epitope of an activated form of BM-40/SPARC/osteonectin. EMBO J. 1998, 17, 1625–1634.
  9. Welcker, D.; Stein, C.; Feitosa, N.M.; Armistead, J.; Zhang, J.L.; Lutke, S.; Kleinridders, A.; Bruning, J.C.; Eming, S.A.; Sengle, G.; et al. Hemicentin-1 is an essential extracellular matrix component of the dermal-epidermal and myotendinous junctions. Sci. Rep. 2021, 11, 17926.
  10. Zhang, J.L.; Richetti, S.; Ramezani, T.; Welcker, D.; Lutke, S.; Pogoda, H.M.; Hatzold, J.; Zaucke, F.; Keene, D.R.; Bloch, W.; et al. Vertebrate extracellular matrix protein hemicentin-1 interacts physically and genetically with basement membrane protein nidogen-2. Matrix Biol. 2022, 112, 132–154.
  11. Wight, T.N.; Raugi, G.J.; Mumby, S.M.; Bornstein, P. Light microscopic immunolocation of thrombospondin in human tissues. J. Histochem. Cytochem. 1985, 33, 295–302.
  12. Bozo, R.; Szel, E.; Danis, J.; Guban, B.; Bata-Csorgo, Z.; Szabo, K.; Kemeny, L.; Groma, G. Cartilage Oligomeric Matrix Protein Negatively Influences Keratinocyte Proliferation via alpha5beta1-Integrin: Potential Relevance of Altered Cartilage Oligomeric Matrix Protein Expression in Psoriasis. J. Investig. Dermatol. 2020, 140, 1733–1742.e7.
  13. Bradshaw, A.D. The role of SPARC in extracellular matrix assembly. J. Cell Commun. Signal. 2009, 3, 239–246.
  14. Detmar, M. The role of VEGF and thrombospondins in skin angiogenesis. J. Dermatol. Sci. 2000, 24 (Suppl. 1), S78–S84.
  15. Streit, M.; Velasco, P.; Brown, L.F.; Skobe, M.; Richard, L.; Riccardi, L.; Lawler, J.; Detmar, M. Overexpression of thrombospondin-1 decreases angiogenesis and inhibits the growth of human cutaneous squamous cell carcinomas. Am. J. Pathol. 1999, 155, 441–452.
  16. Ghetti, M.; Topouzi, H.; Theocharidis, G.; Papa, V.; Williams, G.; Bondioli, E.; Cenacchi, G.; Connelly, J.T.; Higgins, C.A. Subpopulations of dermal skin fibroblasts secrete distinct extracellular matrix: Implications for using skin substitutes in the clinic. Br. J. Dermatol. 2018, 179, 381–393.
  17. Hunzelmann, N.; Hafner, M.; Anders, S.; Krieg, T.; Nischt, R. BM-40 (osteonectin, SPARC) is expressed both in the epidermal and in the dermal compartment of adult human skin. J. Investig. Dermatol. 1998, 110, 122–126.
  18. Wrana, J.L.; Overall, C.M.; Sodek, J. Regulation of the expression of a secreted acidic protein rich in cysteine (SPARC) in human fibroblasts by transforming growth factor beta. Comparison of transcriptional and post-transcriptional control with fibronectin and type I collagen. Eur. J. Biochem. 1991, 197, 519–528.
  19. Ford, R.; Wang, G.; Jannati, P.; Adler, D.; Racanelli, P.; Higgins, P.J.; Staiano-Coico, L. Modulation of SPARC expression during butyrate-induced terminal differentiation of cultured human keratinocytes: Regulation via a TGF-beta-dependent pathway. Exp. Cell Res. 1993, 206, 261–275.
  20. Agarwal, P.; Zwolanek, D.; Keene, D.R.; Schulz, J.N.; Blumbach, K.; Heinegard, D.; Zaucke, F.; Paulsson, M.; Krieg, T.; Koch, M.; et al. Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure. J. Biol. Chem. 2012, 287, 22549–22559.
  21. Siriwach, R.; Ngo, A.Q.; Higuchi, M.; Arima, K.; Sakamoto, S.; Watanabe, A.; Narumiya, S.; Thumkeo, D. Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing. iScience 2022, 25, 104130.
  22. Hsu, Y.C.; Fuchs, E. Building and Maintaining the Skin. Cold Spring Harb. Perspect. Biol. 2022, 14, a040840.
  23. Domingues, L.; Hurbain, I.; Gilles-Marsens, F.; Sires-Campos, J.; Andre, N.; Dewulf, M.; Romao, M.; Viaris de Lesegno, C.; Mace, A.S.; Blouin, C.; et al. Coupling of melanocyte signaling and mechanics by caveolae is required for human skin pigmentation. Nat. Commun. 2020, 11, 2988.
  24. Fukunaga-Kalabis, M.; Martinez, G.; Liu, Z.J.; Kalabis, J.; Mrass, P.; Weninger, W.; Firth, S.M.; Planque, N.; Perbal, B.; Herlyn, M. CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. J. Cell Biol. 2006, 175, 563–569.
  25. Fukunaga-Kalabis, M.; Santiago-Walker, A.; Herlyn, M. Matricellular proteins produced by melanocytes and melanomas: In search for functions. Cancer Microenviron. 2008, 1, 93–102.
  26. Rognoni, E.; Watt, F.M. Skin Cell Heterogeneity in Development, Wound Healing, and Cancer. Trends Cell Biol. 2018, 28, 709–722.
  27. Sabatelli, P.; Gara, S.K.; Grumati, P.; Urciuolo, A.; Gualandi, F.; Curci, R.; Squarzoni, S.; Zamparelli, A.; Martoni, E.; Merlini, L.; et al. Expression of the collagen VI alpha5 and alpha6 chains in normal human skin and in skin of patients with collagen VI-related myopathies. J. Investig. Dermatol. 2011, 131, 99–107.
  28. Watt, F.M.; Fujiwara, H. Cell-extracellular matrix interactions in normal and diseased skin. Cold Spring Harb. Perspect. Biol. 2011, 3, a005124.
  29. Pfisterer, K.; Shaw, L.E.; Symmank, D.; Weninger, W. The Extracellular Matrix in Skin Inflammation and Infection. Front. Cell Dev. Biol. 2021, 9, 682414.
  30. Huang, J.; Heng, S.; Zhang, W.; Liu, Y.; Xia, T.; Ji, C.; Zhang, L.J. Dermal extracellular matrix molecules in skin development, homeostasis, wound regeneration and diseases. Semin. Cell Dev. Biol. 2022, 128, 137–144.
  31. Martino, M.M.; Tortelli, F.; Mochizuki, M.; Traub, S.; Ben-David, D.; Kuhn, G.A.; Muller, R.; Livne, E.; Eming, S.A.; Hubbell, J.A. Engineering the growth factor microenvironment with fibronectin domains to promote wound and bone tissue healing. Sci. Transl. Med. 2011, 3, 100ra189.
  32. Cescon, M.; Gattazzo, F.; Chen, P.; Bonaldo, P. Collagen VI at a glance. J. Cell Sci. 2015, 128, 3525–3531.
  33. Lettmann, S.; Bloch, W.; Maass, T.; Niehoff, A.; Schulz, J.N.; Eckes, B.; Eming, S.A.; Bonaldo, P.; Paulsson, M.; Wagener, R. Col6a1 null mice as a model to study skin phenotypes in patients with collagen VI related myopathies: Expression of classical and novel collagen VI variants during wound healing. PLoS ONE 2014, 9, e105686.
  34. Reinhardt, D.P.; Sasaki, T.; Dzamba, B.J.; Keene, D.R.; Chu, M.L.; Gohring, W.; Timpl, R.; Sakai, L.Y. Fibrillin-1 and fibulin-2 interact and are colocalized in some tissues. J. Biol. Chem. 1996, 271, 19489–19496.
  35. Lemaire, R.; Korn, J.H.; Schiemann, W.P.; Lafyatis, R. Fibulin-2 and fibulin-5 alterations in tsk mice associated with disorganized hypodermal elastic fibers and skin tethering. J. Investig. Dermatol. 2004, 123, 1063–1069.
  36. Midwood, K.S.; Chiquet, M.; Tucker, R.P.; Orend, G. Tenascin-C at a glance. J. Cell Sci. 2016, 129, 4321–4327.
  37. Swindle, C.S.; Tran, K.T.; Johnson, T.D.; Banerjee, P.; Mayes, A.M.; Griffith, L.; Wells, A. Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor. J. Cell Biol. 2001, 154, 459–468.
  38. Schalkwijk, J.; Steijlen, P.M.; van Vlijmen-Willems, I.M.; Oosterling, B.; Mackie, E.J.; Verstraeten, A.A. Tenascin expression in human dermis is related to epidermal proliferation. Am. J. Pathol. 1991, 139, 1143–1150.
  39. Hendaoui, I.; Tucker, R.P.; Zingg, D.; Bichet, S.; Schittny, J.; Chiquet-Ehrismann, R. Tenascin-C is required for normal Wnt/beta-catenin signaling in the whisker follicle stem cell niche. Matrix Biol. 2014, 40, 46–53.
  40. De Laporte, L.; Rice, J.J.; Tortelli, F.; Hubbell, J.A. Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain. PLoS ONE 2013, 8, e62076.
  41. Martino, M.M.; Briquez, P.S.; Guc, E.; Tortelli, F.; Kilarski, W.W.; Metzger, S.; Rice, J.J.; Kuhn, G.A.; Muller, R.; Swartz, M.A.; et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 2014, 343, 885–888.
  42. Kuwatsuka, Y.; Murota, H. Involvement of Periostin in Skin Function and the Pathogenesis of Skin Diseases. Adv. Exp. Med. Biol. 2019, 1132, 89–98.
  43. Egbert, M.; Ruetze, M.; Sattler, M.; Wenck, H.; Gallinat, S.; Lucius, R.; Weise, J.M. The matricellular protein periostin contributes to proper collagen function and is downregulated during skin aging. J. Dermatol. Sci. 2014, 73, 40–48.
  44. Taniguchi, K.; Arima, K.; Masuoka, M.; Ohta, S.; Shiraishi, H.; Ontsuka, K.; Suzuki, S.; Inamitsu, M.; Yamamoto, K.I.; Simmons, O.; et al. Periostin controls keratinocyte proliferation and differentiation by interacting with the paracrine IL-1alpha/IL-6 loop. J. Investig. Dermatol. 2014, 134, 1295–1304.
  45. Zhang, X.; Alanazi, Y.F.; Jowitt, T.A.; Roseman, A.M.; Baldock, C. Elastic Fibre Proteins in Elastogenesis and Wound Healing. Int. J. Mol. Sci. 2022, 23, 4087.
  46. Hucthagowder, V.; Sausgruber, N.; Kim, K.H.; Angle, B.; Marmorstein, L.Y.; Urban, Z. Fibulin-4: A novel gene for an autosomal recessive cutis laxa syndrome. Am. J. Hum. Genet. 2006, 78, 1075–1080.
  47. Markova, D.; Zou, Y.Q.; Ringpfeil, F.; Sasaki, T.; Kostka, G.; Timpl, R.; Uitto, J.; Chu, M.L. Genetic heterogeneity of cutis laxa: A heterozygous tandem duplication within the fibulin-5 (FBLN5) gene. Am. J. Hum. Genet. 2003, 72, 998–1004.
  48. Yanagisawa, H.; Davis, E.C.; Starcher, B.C.; Ouchi, T.; Yanagisawa, M.; Richardson, J.A.; Olson, E.N. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 2002, 415, 168–171.
  49. Rosini, S.; Pugh, N.; Bonna, A.M.; Hulmes, D.J.S.; Farndale, R.W.; Adams, J.C. Thrombospondin-1 promotes matrix homeostasis by interacting with collagen and lysyl oxidase precursors and collagen cross-linking sites. Sci. Signal. 2018, 11, eaar2566.
  50. Kyriakides, T.R.; Zhu, Y.H.; Smith, L.T.; Bain, S.D.; Yang, Z.; Lin, M.T.; Danielson, K.G.; Iozzo, R.V.; LaMarca, M.; McKinney, C.E.; et al. Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J. Cell Biol. 1998, 140, 419–430.
  51. Bradshaw, A.D.; Puolakkainen, P.; Dasgupta, J.; Davidson, J.M.; Wight, T.N.; Helene Sage, E. SPARC-null mice display abnormalities in the dermis characterized by decreased collagen fibril diameter and reduced tensile strength. J. Investig. Dermatol. 2003, 120, 949–955.
  52. Bradshaw, A.D.; Graves, D.C.; Motamed, K.; Sage, E.H. SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc. Natl. Acad. Sci. USA 2003, 100, 6045–6050.
  53. Bradshaw, A.D.; Reed, M.J.; Sage, E.H. SPARC-null mice exhibit accelerated cutaneous wound closure. J. Histochem. Cytochem. 2002, 50, 1–10.
  54. Tremblay, F.; Revett, T.; Huard, C.; Zhang, Y.; Tobin, J.F.; Martinez, R.V.; Gimeno, R.E. Bidirectional modulation of adipogenesis by the secreted protein Ccdc80/DRO1/URB. J. Biol. Chem. 2009, 284, 8136–8147.
  55. Okada, T.; Nishizawa, H.; Kurata, A.; Tamba, S.; Sonoda, M.; Yasui, A.; Kuroda, Y.; Hibuse, T.; Maeda, N.; Kihara, S.; et al. URB is abundantly expressed in adipose tissue and dysregulated in obesity. Biochem. Biophys. Res. Commun. 2008, 367, 370–376.
  56. Grill, J.I.; Neumann, J.; Herbst, A.; Ofner, A.; Hiltwein, F.; Marschall, M.K.; Zierahn, H.; Wolf, E.; Schneider, M.R.; Kolligs, F.T. Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation. Mol. Cell. Endocrinol. 2017, 439, 286–296.
  57. Zhang, H.Y.; Timpl, R.; Sasaki, T.; Chu, M.L.; Ekblom, P. Fibulin-1 and fibulin-2 expression during organogenesis in the developing mouse embryo. Dev. Dyn. 1996, 205, 348–364.
  58. Fujiwara, H.; Ferreira, M.; Donati, G.; Marciano, D.K.; Linton, J.M.; Sato, Y.; Hartner, A.; Sekiguchi, K.; Reichardt, L.F.; Watt, F.M. The basement membrane of hair follicle stem cells is a muscle cell niche. Cell 2011, 144, 577–589.
  59. Wang, T.; Wagner, A.; Gehwolf, R.; Yan, W.; Passini, F.S.; Thien, C.; Weissenbacher, N.; Lin, Z.; Lehner, C.; Teng, H.; et al. Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries. Sci. Transl. Med. 2021, 13, eabe5738.
  60. Wang, Y.; Jin, S.; Luo, D.; He, D.; Shi, C.; Zhu, L.; Guan, B.; Li, Z.; Zhang, T.; Zhou, Y.; et al. Functional regeneration and repair of tendons using biomimetic scaffolds loaded with recombinant periostin. Nat. Commun. 2021, 12, 1293.
  61. Jarvinen, T.A.; Jozsa, L.; Kannus, P.; Jarvinen, T.L.; Hurme, T.; Kvist, M.; Pelto-Huikko, M.; Kalimo, H.; Jarvinen, M. Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle. J. Cell Sci. 2003, 116, 857–866.
  62. Sipila, K.; Rognoni, E.; Jokinen, J.; Tewary, M.; Vietri Rudan, M.; Talvi, S.; Jokinen, V.; Dahlstrom, K.M.; Liakath-Ali, K.; Mobasseri, A.; et al. Embigin is a fibronectin receptor that affects sebaceous gland differentiation and metabolism. Dev. Cell 2022, 57, 1453–1465.e7.
  63. Chen, D.; Chen, X.; Xie, H.T.; Hatton, M.P.; Liu, X.; Liu, Y. Expression of extracellular matrix components in the meibomian gland. Front. Med. 2022, 9, 981610.
  64. Igoucheva, O.; Alexeev, V.; Halabi, C.M.; Adams, S.M.; Stoilov, I.; Sasaki, T.; Arita, M.; Donahue, A.; Mecham, R.P.; Birk, D.E.; et al. Fibulin-4 E57K Knock-in Mice Recapitulate Cutaneous, Vascular and Skeletal Defects of Recessive Cutis Laxa 1B with both Elastic Fiber and Collagen Fibril Abnormalities. J. Biol. Chem. 2015, 290, 21443–21459.
  65. Nakamura, T.; Lozano, P.R.; Ikeda, Y.; Iwanaga, Y.; Hinek, A.; Minamisawa, S.; Cheng, C.F.; Kobuke, K.; Dalton, N.; Takada, Y.; et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 2002, 415, 171–175.
  66. Rognoni, E.; Pisco, A.O.; Hiratsuka, T.; Sipila, K.H.; Belmonte, J.M.; Mobasseri, S.A.; Philippeos, C.; Dilao, R.; Watt, F.M. Fibroblast state switching orchestrates dermal maturation and wound healing. Mol. Syst. Biol. 2018, 14, e8174.
  67. Lynch, M.D.; Watt, F.M. Fibroblast heterogeneity: Implications for human disease. J. Clin. Investig. 2018, 128, 26–35.
  68. Ganier, C.; Rognoni, E.; Goss, G.; Lynch, M.; Watt, F.M. Fibroblast Heterogeneity in Healthy and Wounded Skin. Cold Spring Harb. Perspect. Biol. 2022, 14, a041238.
  69. Chen, S.X.; Zhang, L.J.; Gallo, R.L. Dermal White Adipose Tissue: A Newly Recognized Layer of Skin Innate Defense. J. Investig. Dermatol. 2019, 139, 1002–1009.
  70. Zhang, L.J.; Guerrero-Juarez, C.F.; Hata, T.; Bapat, S.P.; Ramos, R.; Plikus, M.V.; Gallo, R.L. Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 2015, 347, 67–71.
  71. Sillat, T.; Saat, R.; Pollanen, R.; Hukkanen, M.; Takagi, M.; Konttinen, Y.T. Basement membrane collagen type IV expression by human mesenchymal stem cells during adipogenic differentiation. J. Cell. Mol. Med. 2012, 16, 1485–1495.
  72. Mariman, E.C.; Wang, P. Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell. Mol. Life Sci. 2010, 67, 1277–1292.
  73. Reggio, S.; Rouault, C.; Poitou, C.; Bichet, J.C.; Prifti, E.; Bouillot, J.L.; Rizkalla, S.; Lacasa, D.; Tordjman, J.; Clement, K. Increased Basement Membrane Components in Adipose Tissue during Obesity: Links with TGFbeta and Metabolic Phenotypes. J. Clin. Endocrinol. Metab. 2016, 101, 2578–2587.
  74. Mori, S.; Kiuchi, S.; Ouchi, A.; Hase, T.; Murase, T. Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue. Int. J. Biol. Sci. 2014, 10, 825–833.
  75. McCulloch, L.J.; Rawling, T.J.; Sjoholm, K.; Franck, N.; Dankel, S.N.; Price, E.J.; Knight, B.; Liversedge, N.H.; Mellgren, G.; Nystrom, F.; et al. COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity. Endocrinology 2015, 156, 134–146.
  76. Bolton, K.; Segal, D.; McMillan, J.; Jowett, J.; Heilbronn, L.; Abberton, K.; Zimmet, P.; Chisholm, D.; Collier, G.; Walder, K. Decorin is a secreted protein associated with obesity and type 2 diabetes. Int. J. Obes. 2008, 32, 1113–1121.
  77. Han, C.Y.; Kang, I.; Harten, I.A.; Gebe, J.A.; Chan, C.K.; Omer, M.; Alonge, K.M.; den Hartigh, L.J.; Gomes Kjerulf, D.; Goodspeed, L.; et al. Adipocyte-Derived Versican and Macrophage-Derived Biglycan Control Adipose Tissue Inflammation in Obesity. Cell Rep. 2020, 31, 107818.
  78. Daquinag, A.C.; Gao, Z.; Fussell, C.; Sun, K.; Kolonin, M.G. Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly. Cells 2020, 9, 2646.
  79. Joost, S.; Annusver, K.; Jacob, T.; Sun, X.; Dalessandri, T.; Sivan, U.; Sequeira, I.; Sandberg, R.; Kasper, M. The Molecular Anatomy of Mouse Skin during Hair Growth and Rest. Cell Stem Cell 2020, 26, 441–457.e7.
  80. Blanpain, C.; Lowry, W.E.; Geoghegan, A.; Polak, L.; Fuchs, E. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 2004, 118, 635–648.
  81. Rahmani, W.; Abbasi, S.; Hagner, A.; Raharjo, E.; Kumar, R.; Hotta, A.; Magness, S.; Metzger, D.; Biernaskie, J. Hair follicle dermal stem cells regenerate the dermal sheath, repopulate the dermal papilla, and modulate hair type. Dev. Cell 2014, 31, 543–558.
  82. Clavel, C.; Grisanti, L.; Zemla, R.; Rezza, A.; Barros, R.; Sennett, R.; Mazloom, A.R.; Chung, C.Y.; Cai, X.; Cai, C.L.; et al. Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors. Dev. Cell 2012, 23, 981–994.
  83. Ng, K.J.; Lim, J.; Tan, Y.N.; Quek, D.; Lim, Z.; Pantelireis, N.; Clavel, C. Sox2 in the dermal papilla regulates hair follicle pigmentation. Cell Rep. 2022, 40, 111100.
  84. Greco, V.; Chen, T.; Rendl, M.; Schober, M.; Pasolli, H.A.; Stokes, N.; Dela Cruz-Racelis, J.; Fuchs, E. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell 2009, 4, 155–169.
  85. Harshuk-Shabso, S.; Dressler, H.; Niehrs, C.; Aamar, E.; Enshell-Seijffers, D. Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock. Nat. Commun. 2020, 11, 5114.
  86. Tsutsui, K.; Machida, H.; Nakagawa, A.; Ahn, K.; Morita, R.; Sekiguchi, K.; Miner, J.H.; Fujiwara, H. Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions. Nat. Commun. 2021, 12, 2577.
  87. Morris, R.J.; Liu, Y.; Marles, L.; Yang, Z.; Trempus, C.; Li, S.; Lin, J.S.; Sawicki, J.A.; Cotsarelis, G. Capturing and profiling adult hair follicle stem cells. Nat. Biotechnol. 2004, 22, 411–417.
  88. Timpl, R.; Brown, J.C. The laminins. Matrix Biol. 1994, 14, 275–281.
  89. Niemann, C.; Horsley, V. Development and homeostasis of the sebaceous gland. Semin. Cell Dev. Biol. 2012, 23, 928–936.
  90. Geueke, A.; Niemann, C. Stem and progenitor cells in sebaceous gland development, homeostasis and pathologies. Exp. Dermatol. 2021, 30, 588–597.
  91. Kobayashi, T.; Voisin, B.; Kim, D.Y.; Kennedy, E.A.; Jo, J.H.; Shih, H.Y.; Truong, A.; Doebel, T.; Sakamoto, K.; Cui, C.Y.; et al. Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium. Cell 2019, 176, 982–997.e16.
  92. Thiele, J.J.; Weber, S.U.; Packer, L. Sebaceous gland secretion is a major physiologic route of vitamin E delivery to skin. J. Investig. Dermatol. 1999, 113, 1006–1010.
  93. Nishiyama, T.; Kii, I.; Kashima, T.G.; Kikuchi, Y.; Ohazama, A.; Shimazaki, M.; Fukayama, M.; Kudo, A. Delayed re-epithelialization in periostin-deficient mice during cutaneous wound healing. PLoS ONE 2011, 6, e18410.
  94. Liu, S.; Leask, A. CCN2 modulates hair follicle cycling in mice. Mol. Biol. Cell 2013, 24, 3939–3944.
  95. Smith, A.A.; Li, J.; Liu, B.; Hunter, D.; Pyles, M.; Gillette, M.; Dhamdhere, G.R.; Abo, A.; Oro, A.; Helms, J.A. Activating Hair Follicle Stem Cells via R-spondin2 to Stimulate Hair Growth. J. Investig. Dermatol. 2016, 136, 1549–1558.
  96. Hagner, A.; Shin, W.; Sinha, S.; Alpaugh, W.; Workentine, M.; Abbasi, S.; Rahmani, W.; Agabalyan, N.; Sharma, N.; Sparks, H.; et al. Transcriptional Profiling of the Adult Hair Follicle Mesenchyme Reveals R-spondin as a Novel Regulator of Dermal Progenitor Function. iScience 2020, 23, 101019.
  97. Ge, Y.; Miao, Y.; Gur-Cohen, S.; Gomez, N.; Yang, H.; Nikolova, M.; Polak, L.; Hu, Y.; Verma, A.; Elemento, O.; et al. The aging skin microenvironment dictates stem cell behavior. Proc. Natl. Acad. Sci. USA 2020, 117, 5339–5350.
  98. Yano, K.; Brown, L.F.; Lawler, J.; Miyakawa, T.; Detmar, M. Thrombospondin-1 plays a critical role in the induction of hair follicle involution and vascular regression during the catagen phase. J. Investig. Dermatol. 2003, 120, 14–19.
  99. Naldaiz-Gastesi, N.; Bahri, O.A.; Lopez de Munain, A.; McCullagh, K.J.A.; Izeta, A. The panniculus carnosus muscle: An evolutionary enigma at the intersection of distinct research fields. J. Anat. 2018, 233, 275–288.
  100. Naldaiz-Gastesi, N.; Goicoechea, M.; Alonso-Martin, S.; Aiastui, A.; Lopez-Mayorga, M.; Garcia-Belda, P.; Lacalle, J.; San Jose, C.; Arauzo-Bravo, M.J.; Trouilh, L.; et al. Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells. Stem Cell Rep. 2016, 7, 411–424.
  101. Machado, M.J.; Watson, M.G.; Devlin, A.H.; Chaplain, M.A.; McDougall, S.R.; Mitchell, C.A. Dynamics of angiogenesis during wound healing: A coupled in vivo and in silico study. Microcirculation 2011, 18, 183–197.
  102. Pratt, R.L. Hyaluronan and the Fascial Frontier. Int. J. Mol. Sci. 2021, 22, 6845.
  103. Fede, C.; Pirri, C.; Fan, C.; Petrelli, L.; Guidolin, D.; De Caro, R.; Stecco, C. A Closer Look at the Cellular and Molecular Components of the Deep/Muscular Fasciae. Int. J. Mol. Sci. 2021, 22, 1411.
  104. Stecco, C.; Fede, C.; Macchi, V.; Porzionato, A.; Petrelli, L.; Biz, C.; Stern, R.; De Caro, R. The fasciacytes: A new cell devoted to fascial gliding regulation. Clin. Anat. 2018, 31, 667–676.
  105. McLaughlin, P.J.; Bakall, B.; Choi, J.; Liu, Z.; Sasaki, T.; Davis, E.C.; Marmorstein, A.D.; Marmorstein, L.Y. Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. Hum. Mol. Genet. 2007, 16, 3059–3070.
  106. Driver, S.G.W.; Jackson, M.R.; Richter, K.; Tomlinson, P.; Brockway, B.; Halliday, B.J.; Markie, D.M.; Robertson, S.P.; Wade, E.M. Biallelic variants in EFEMP1 in a man with a pronounced connective tissue phenotype. Eur. J. Hum. Genet. 2020, 28, 445–452.
  107. Correa-Gallegos, D.; Jiang, D.; Christ, S.; Ramesh, P.; Ye, H.; Wannemacher, J.; Kalgudde Gopal, S.; Yu, Q.; Aichler, M.; Walch, A.; et al. Patch repair of deep wounds by mobilized fascia. Nature 2019, 576, 287–292.
  108. Jiang, D.; Christ, S.; Correa-Gallegos, D.; Ramesh, P.; Kalgudde Gopal, S.; Wannemacher, J.; Mayr, C.H.; Lupperger, V.; Yu, Q.; Ye, H.; et al. Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin. Nat. Commun. 2020, 11, 5653.
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