You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Matrix Metalloproteinase-10: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Allergy
Contributor: Sun xiaoli

Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase with the ability to degrade a broad spectrum of extracellular matrices and other protein substrates. The expression of MMP-10 is induced in acute kidney injury (AKI) and chronic kidney disease (CKD), as well as in renal cell carcinoma (RCC). During the different stages of kidney injury, MMP-10 may exert distinct functions by cleaving various bioactive substrates including heparin-binding epidermal growth factor (HB-EGF), zonula occludens-1 (ZO-1), and pro-MMP-1, -7, -8, -9, -10, -13. Functionally, MMP-10 is reno-protective in AKI by promoting HB-EGF-mediated tubular repair and regeneration, whereas it aggravates podocyte dysfunction and proteinuria by disrupting glomerular filtration integrity via degrading ZO-1. 

  • MMP-10
  • acute kidney injury
  • chronic kidney disease

1. Biology of Matrix Metalloproteinase-10 (MMP-10)

Matrix metalloproteinase-10 (MMP-10) belongs to a large family of MMPs consisting of 25 known members [1]. MMP-10 shares common structural motifs with other MMPs. MMP-10 activities are modulated on several levels including transcription, pro-enzyme activation, or inhibition by its inhibitors.

1.1. Structure of MMP-10

As a secreted protein, MMP-10 is primarily synthesized as the 476 amino acid zymogen comprised of four domains: 17 amino acid N-terminal signal peptide, 81 amino acid pro-peptide domain, 165 amino acid catalytic domain, and 187 amino acid hemopexin domain [2][3][4]. Interestingly, recent studies reveal that a nuclear localization sequence (NLS) might exist in the C-terminal, which contributes MMP-10 to be localized and targeted to the nucleus [5][6][7].
The pro-peptide contains a cysteine switch motif [8], an intramolecular complex formed between the sulfhydryl group of the cysteine residue in the pro-peptide domain and the essential zinc ion located in the catalytic domain. The cysteine switch motif blocks the active site and maintains the precursor structure [2]. Consequently, disruption of this motif can release active enzyme [9].
Two zinc ions (one catalytic and one structural) and three calcium ions are indispensable for the catalytic site. Three histidines from the zinc binding motif in the catalytic domain coordinate with catalytic zinc and constitute the catalytic site [10]. Importantly, the substrate specificity is predominantly determined by the S1′ hydrophobic pocket which is adjacent to the catalytic site [11].
The hemopexin domain with four hemopexin-like repeats presents four-bladed propeller folds which links with the catalytic domain by a flexible hinge region. In addition to regulating protein–protein interaction, the hemopexin domain could play an auxiliary role in helping substrate binding at catalytic sites [12].

1.2. Transcriptional Regulation of MMP-10

In humans, the MMP-10 gene is mapped to chromosomes at 11q22.2. A set of various trans-activators can modulate the expression of MMP-10 by regulating certain cis-elements, including TATA boxes, activated protein-1 (AP-1) binding site, polyoma enhancer activator 3 (PEA3)-binding site, β-catenin/T-cell factor 4 (TCF4), and nuclear factor-ĸB (NF-ĸB) [13][14][15]. The interplay of a variety of cis-acting elements with cognate transcription factors confers the response to specific cues in various tissues and cell types. Moreover, DNA hypomethylation can also modulate transcriptional activity on the MMP-10 promoter in a cell-specific manner [16].
NF-κB and AP-1 are widely activated in all kinds of kidney disorders and participate in the progression of nephropathies [17]. Transforming growth factor-β (TGF-β), a powerful profibrotic cytokine, may transactivate MMP-10 by a specific interaction between the Smad proteins and AP-1 [18]. Furthermore, another study shows that MMP-10 expression is regulated by TGF-β through mediating activation of myocyte enhancer factor 2A (MEF2A) and downregulating class IIα histone deacetylases (HDACs) [19]. In addition, biomechanical stretching also induces MMP-10 expression by mediating NF-ĸB activation in podocytes in vitro [20].
Bioinformatics analysis shows that there are two putative TCF/LEF-binding sites (TBS) in the promoter region of MMP-10 [21]. In various kinds of nephropathies, canonical Wnt/β-catenin signaling is activated and plays a pivotal role in mediating kidney injury, repair and pathogenesis [22][23][24]. Recent studies indicate that Wnt7a induces MMP-10 expression through the canonical β-catenin pathway [21]. Furthermore, overexpression of Wnt5b in vitro upregulates MMP-10 expression as well [25]. As Wnt/β-catenin is activated in all kinds of AKI and CKD examined, these findings suggest a widespread induction of MMP-10 in various kidney disorders.

1.3. Posttranscriptional Activation of MMP-10

MMP-10 is commonly regarded as an extracellular proteinase. However, recent finding shows that MMP-10 is also activated inside the cell and involved in the pathogenesis of diseases [6]. The mechanism by which MMP-10 enters cells has not been fully elucidated. During the activation, pro-MMP-10 is enzymatically cleaved, and its conformation is modified. Pro-MMP-10 is secreted into the extracellular space after the N-terminal signal peptide is removed and can be subsequently activated by various factors [2]. In extracellular milieu, the His81-Phe82 bond in the pro-peptide is often cleaved by other proteolytic enzymes, such as plasma kallikrein, trypsin, neutrophil elastase, or cathepsin G [26][3]. As such, this procedure contributes to the conversion of 56 kDa latent MMP-10 to mature active forms, which are 47 kDa and 24 kDa, respectively [8]. Along with this, the cysteine residue is dissociated from catalytic zinc that leads to cysteine-switch activation, and the catalytic site is exposed [9].
It has been shown that pro-MMP-10 is labile and can undergo autolysis, leading to the production of mature MMP-10 [8]. Under nondenaturing conditions, MMP-10 can also be activated through conformational change without cleavage of the pro-peptide after exposure to SDS [2].

1.4. Inhibitors of MMP-10

Inhibitors of MMP-10 are composed of two classes: endogenous and synthetic. Tissue inhibitors of metalloproteinases (TIMPs), consisting of TIMP1~4, are secreted proteins and function against multiple secreted or membrane-anchored metalloproteinases [27]. In addition, TIMPs play a pivotal role in modulating the influence of the extracellular environment on cell phenotype [28]. It has been demonstrated that each of the TIMPs can inhibit MMP-10 activity by forming a complex in a 1:1 stoichiometry [29][30][31]. In spite of substantial structural differences between the TIMPs, most of the flexible loops of the MMP-10 catalytic domain are locked into nearly indistinguishable conformations upon TIMP binding [30]. Disrupting the balance between MMP-10 and TIMPs will contribute to a broad spectrum of devastating diseases.
Although TIMPs can be considered as MMP-10 endogenous inhibitors, their actions are not merely on MMP-10 [27]. The development of a specific MMP-10 inhibitor with a pure inhibitory spectrum is urgent. Structurally, MMP-10 clearly resembles other MMPs, especially MMP-3, as they share 78% overall amino acid sequence identity and 86% sequence identity in their catalytic domain in humans. This makes it difficult to develop a selective and potent MMP-10 inhibitor [3][10]. Nevertheless, there are several studies reporting that selective dual MMP-10/-13 inhibitors possess a clean inhibition profile and outstanding affinity for MMP-10 [32][33]. Furthermore, MMP-10 activity can be regulated by increased or diminished expression at the transcriptional or translational levels. Synthetic inhibitors generally contain a chelating group that binds the catalytic zinc atom at the MMP active site. Other inhibitors interact with various binding pockets on the MMP of interest resulting in specific inhibitory potentials for the given MMP. In addition, single-domain antibodies devoid of a light chain and CH1 region emerge as attractive inhibitors [34]. A recent study reported a single-domain antibody, H3, which can selectively inhibit MMP-10 activity by binding to its active site [35]. Further studies on developing specific inhibitors of MMP-10 are needed to provide a novel therapeutic strategy for various diseases with hyperactive MMP-10.

2. MMP-10 Expression in the Kidney

Contrary to its weak staining in normal human kidney tubular cells [36], MMP-10 is scarcely expressed in normal murine kidneys. It is substantially induced under pathological conditions [37][38]. Consistently, MMP-10-/- mice and transgenic mice with podocyte-specific expression of MMP-10 do not display overt renal abnormality [37][39]. These findings indicate that MMP-10 is not required for murine kidney structure and function under normal physiological conditions. However, overexpression of MMP-10 renders transgenic mice susceptible to developing more severe podocytopathy after injury [37].
In response to diverse insults, MMP-10 can be induced in various cells, including the renal tubular epithelium, glomerular podocytes, juxtaglomerular apparatus, as well as renal cell carcinoma [37][38][36][40].

2.1. AKI

Induction of MMP-10 is a common pathological finding in various models of AKI. Studies show that MMP-10 protein is substantially upregulated in various animal models of AKI, including ischemia-reperfusion injury (IRI), cisplatin-induced nephrotoxic AKI and glycerol-induced rhabdomyolysis-associated AKI [38][41]. Notably, the mRNA level of MMP-10 is induced as early as 4 h and sustained at least to 48 h after IRI [38]. Data mining from the Kidney Interactive Transcriptomics database created by single-nuclei RNA-sequencing reveals the dynamics and landscape of MMP-10 expression in mouse AKI induced by IRI (http://humphreyslab.com/SingleCell, accessed on 20 December 2021). Furthermore, proximal tubules, especially the S3 segment, are the main cell population that express MMP-10 following IRI[42]. Immunohistochemical staining reveals that MMP-10 is strongly stained in the injured area of the kidney and predominantly localizes in the renal tubular epithelium [38][41]. The mechanism underlying MMP-10 induction in AKI, as well as the triggers for induction, remains unclear. Notably, the canonical Wnt/β-catenin signaling, which protects the kidney from AKI [43], is activated in this setting. This may account for the regulatory mechanism of MMP-10 expression in response to AKI.

2.2. CKD

MMP-10 can also be detected in the glomerular podocytes of CKD patients with diabetic kidney disease (DKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS) [37]. Consistent with this finding, MMP-10 protein is not only induced significantly in adriamycin (ADR) mice in a time-dependent fashion, but is also upregulated in other proteinuric CKD models, such as diabetic db/db mice, remnant kidney model after 5/6 nephrectomy (5/6NX), Alport mice, CD151 null mice and α-actinin-4 knockout mice, which are a Alport syndrome model and a model of FSGS, respectively [37][20][40][44]. Furthermore, compared with the controls, zymographic analysis also reveals an increase in MMP-10 proteolytic activity in the kidney after ADR [37]. In experimental models, MMP-10 is not only localized in glomerular podocytes but also in the juxtaglomerular apparatus [37][40][45].

2.3. RCC

Upregulation of MMP-10 is also common in numerous cancers [46]. In patients with renal cell carcinoma (RCC), immunohistochemical staining reveals that induction of MMP-10 is primarily detected in tubular cancer cell cytoplasm [36]. Meanwhile, MMP-10 expression exhibits a tight correlation with the grade and pT stage. Cancer cells of the invasive front strongly express MMP-10, and the majority of sarcomatous cancer cells shows moderate or strong intensity [36]. As such, sarcomatous change represents a transformation to a higher-grade malignancy and portends a worse prognosis in renal cell carcinoma [47]. Consequently, these findings suggest that MMP-10 is relevant to RCC invasion.
MMP-10 appears to be the target of diverse factors involved in RCC invasion. In favor of this notion, ghrelin, a peptide hormone, binds to the ghrelin receptor and results in MMP-10 expression by upregulating Aurora A, which results in RCC invasion [48]. In vitro, MMP-10 is upregulated by IL-1β, mechanistically due to activation of transcription factor CCAAT enhancer binding protein β (CEBPβ) [49]. In addition, there is a study reporting that activation of MMP-10 might be involved in the secreted frizzled-related protein 1 (SFRP1)-caused cell invasion in metastatic RCC [50].

3. Mechanism of MMP-10 Action in Kidney Disease

3.1. HB-EGF

HB-EGF is a membrane-anchored growth factor, which is widely expressed in glomerular and tubular compartments of adult kidneys at a very low level. In response to AKI, HB-EGF is markedly induced primarily in tubular epithelial cells [51]. As a unique epidermal growth factor receptor (EGFR) ligand, HB-EGF is activated post-translationally after cleavage of its ectodomain by diverse proteinases [52]. Activated HB-EGF then binds to EGFR and promotes renal epithelial cell repair, proliferation, and regeneration after injury [51][52]. Recent studies identify MMP-10 as the key enzyme responsible for mediating the cleavage of HB-EGF in human proximal tubular cells. As such, MMP-10 releases an active HB-EGF fragment capable of binding to EGFR, which prevents human proximal tubular epithelial cells from hypoxia-reoxygenation (H/R)-induced injury in vitro [38]. The beneficial role of MMP-10 in AKI is in harmony with many earlier reports in which activation of EGFR signaling is vital for renal tubular injury repair and regeneration [53][54][55]. In agreement with this notion, the protective role of MMP-10 in AKI can be eradicated by erlotinib, a specific EGFR tyrosine kinase inhibitor [38][56].
Like EGFR, the role of the MMP-10/HB-EGF/EGFR axis in renal pathology is somehow contradictory and context-dependent, as both beneficial and deleterious effects have been reported in the kidney [57][58][59]. In addition to the protective role illustrated above, mounting evidence suggests that persistent tubule-specific EGFR activation contributes to renal fibrosis in response to chronic injury [60][61][62]. Furthermore, transgenic mice that selectively express human HB-EGF in the proximal tubule develop spontaneous, early onset, progressive tubulointerstitial fibrosis [63]. Mechanistically, activation of EGFR stimulates signal transduction and activator of transcription (STAT3), which interacts with the promoter region of homeodomain-interacting protein kinase 2 (HIPK2) gene and drives the progression of AKI to CKD [64]. These findings raise an intriguing possibility that MMP-10 facilitates tubulointerstitial fibrosis by cleaving HB-EGF, leading to activation of EGFR in the renal proximal tubule.

3.2. ZO-1

ZO-1 is a tight junctional protein that constitutes the framework of podocyte junctions and plays an indispensable role in nephrogenesis and maintaining renal function [65][66][67]. The expression of ZO-1 in podocytes and its interaction with slit diaphragm components, such as nephrin, NEPH1 and NEPH3, are critical for maintaining the integrity of the filtration barrier of glomeruli [66][68]. A recent study indicates that MMP-10 specifically cleaves ZO-1, thereby impairing the integrity of slit diaphragm and resulting in podocyte dysfunction and proteinuria [37]. This finding is in line with an earlier report demonstrating that specific loss of ZO-1 in podocytes leads to proteinuria and renal dysfunction with impaired glomerular filtration [69].
As a key tight junctional protein, ZO-1 has a function in modulating paracellular permeability by interacting with ZO-1-associated nucleic acid binding protein (ZONAB), a Y-box transcription factor, normally bound to the SH3 domain of ZO-1 at intercellular tight junctions [70][71][72]. In this regard, ZO-1 might also function as an inhibitor of ZONAB [73]. The interaction between ZO-1 and ZONAB is essential for maintaining barrier function of epithelia and regulating epithelial cell proliferation and differentiation [74][75]. Destruction of ZO-1/ZONAB complex leads to nuclear translocation of ZONAB from tight junctions, resulting in target gene expression [76].
Although prior work has focused primarily on the role of ZO-1 in slit diaphragm, it has been demonstrated that ZO-1 is also abundantly expressed in renal tubule epithelial cells [66][77][78]. The ZO-1/ZONAB signal pathway is indispensable for modulating epithelial phenotype. Certainly, following separation of ZONAB from ZO-1, nuclear ZONAB is positioned to shift the switch from differentiation to proliferation in proximal tubule epithelial cells in a cell density-dependent manner [79]. Furthermore, ZONAB also promotes the stabilization and enhanced translation of p21 mRNA involved in cellular senescence [80][81]. In nephropathic cystinosis, overproduction of reactive oxygen species (ROS) contributes to the destruction of tight junction integrity and ZONAB nuclear translocation, which is disastrous for renal tubular epithelial function [73][82]. Based on these findings, it is tempting to speculate that the demolition of the tight junction and activation of a signaling cascade involving ZONAB in tubular cells, due to cleavage of ZO-1 by MMP-10, might be another mechanism in the evolution of CKD.

3.3. Other MMPs

As a proteolytic enzyme, MMP-10 is capable of cleaving pro-MMP-7 in a dose- and time-dependent manner, resulting in the release of mature MMP-7 [8]. Moreover, several direct lines of evidence suggest a role for MMP-10 in activating pro-MMP-9 in a dose-dependent manner, which rapidly produces four stable small fragments [83][8]. Of note, the proteolytic capacity of MMP-10 to pro-MMP-9 is more powerful than to pro-MMP-7. Recombinant pro-MMP-1, pro-MMP-8, as well as pro-MMP-13 could also be processed to the mature form by incubating with MMP-10 [26][84]. Of particularly interest, in contrast to a previous report that MMP-10 fails to directly digest pro-MMP-2 [8], a more recent study demonstrates that MMP-10 can cleave the collagen α2 (I) chain through activating an endogenous collagenolytic MMP with the molecular weight similar to activated MMP-2 [85]. Nevertheless, whether this collagenase is MMP-2 needs further investigation.
The expression of MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-10, as well as MMP-13 are upregulated after kidney damage [1][86]. Up to now, studies show all of them implicated in the pathophysiology of kidney disorders [87][88][89]. MMP-8 and MMP-13 have function in reducing kidney fibrosis by promoting matrix degradation after damage [90][91]. Contrary to this conclusion, there is a study showing that a selective MMP-13 inhibitor is able to alleviate renal fibrosis [92]. Taken together, these studies indicate that the ability of MMP-10 to super-activate other MMPs, including pro-MMP-1, pro-MMP-7, pro-MMP-8, pro-MMP-9, pro-MMP-10 and pro-MMP-13, might be another mechanism of MMP-10 involved in renal pathology.

This entry is adapted from the peer-reviewed paper 10.3390/ijms23042131

References

  1. Zakiyanov, O.; Kalousova, M.; Zima, T.; Tesar, V. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in kidney disease. Adv. Clin. Chem. 2021, 105, 141–212.
  2. Windsor, L.J.; Grenett, H.; Birkedal-Hansen, B.; Bodden, M.K.; Engler, J.A.; Birkedal-Hansen, H. Cell type-specific regulation of SL-1 and SL-2 genes. Induction of the SL-2 gene but not the SL-1 gene by human keratinocytes in response to cytokines and phorbolesters. J. Biol. Chem. 1993, 268, 17341–17347.
  3. Muller, D.; Quantin, B.; Gesnel, M.C.; Millon-Collard, R.; Abecassis, J.; Breathnach, R. The collagenase gene family in humans consists of at least four members. Biochem. J. 1988, 253, 187–192.
  4. Tallant, C.; Marrero, A.; Gomis-Rüth, F.X. Matrix metalloproteinases: Fold and function of their catalytic domains. Biochim. Biophys. Acta 2010, 1803, 20–28.
  5. Bassiouni, W.; Ali, M.A.M.; Schulz, R. Multifunctional intracellular matrix metalloproteinases: Implications in disease. FEBS J. 2021, 288, 7162–7182.
  6. Miller, J.P.; Holcomb, J.; Al-Ramahi, I.; de Haro, M.; Gafni, J.; Zhang, N.; Kim, E.; Sanhueza, M.; Torcassi, C.; Kwak, S.; et al. Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington’s disease. Neuron 2010, 67, 199–212.
  7. Kohrmann, A.; Kammerer, U.; Kapp, M.; Dietl, J.; Anacker, J. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer 2009, 9, 188.
  8. Nakamura, H.; Fujii, Y.; Ohuchi, E.; Yamamoto, E.; Okada, Y. Activation of the precursor of human stromelysin 2 and its interactions with other matrix metalloproteinases. Eur. J. Biochem. 1998, 253, 67–75.
  9. Van Wart, H.E.; Birkedal-Hansen, H. The cysteine switch: A principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc. Natl. Acad. Sci. USA 1990, 87, 5578–5582.
  10. Bertini, I.; Calderone, V.; Fragai, M.; Luchinat, C.; Mangani, S.; Terni, B. Crystal structure of the catalytic domain of human matrix metalloproteinase 10. J. Mol. Biol. 2004, 336, 707–716.
  11. Gimeno, A.; Beltrán-Debón, R.; Mulero, M.; Pujadas, G.; Garcia-Vallvé, S. Understanding the variability of the S1’ pocket to improve matrix metalloproteinase inhibitor selectivity profiles. Drug Discov. Today 2020, 25, 38–57.
  12. Andreini, C.; Banci, L.; Bertini, I.; Luchinat, C.; Rosato, A. Bioinformatic comparison of structures and homology-models of matrix metalloproteinases. J. Proteome Res. 2004, 3, 21–31.
  13. Yan, C.; Boyd, D.D. Regulation of matrix metalloproteinase gene expression. J. Cell. Physiol. 2007, 211, 19–26.
  14. Murray, M.Y.; Birkland, T.P.; Howe, J.D.; Rowan, A.D.; Fidock, M.; Parks, W.C.; Gavrilovic, J. Macrophage migration and invasion is regulated by MMP10 expression. PLoS ONE 2013, 8, e63555.
  15. Benbow, U.; Brinckerhoff, C.E. The AP-1 site and MMP gene regulation: What is all the fuss about? Matrix Biol. 1997, 15, 519–526.
  16. Couillard, J.; Demers, M.; Lavoie, G.; St-Pierre, Y. The role of DNA hypomethylation in the control of stromelysin gene expression. Biochem. Biophys. Res. Commun. 2006, 342, 1233–1239.
  17. Mezzano, S.A.; Barría, M.; Droguett, M.A.; Burgos, M.E.; Ardiles, L.G.; Flores, C.; Egido, J. Tubular NF-kappaB and AP-1 activation in human proteinuric renal disease. Kidney Int. 2001, 60, 1366–1377.
  18. Sundqvist, A.; Zieba, A.; Vasilaki, E.; Herrera Hidalgo, C.; Söderberg, O.; Koinuma, D.; Miyazono, K.; Heldin, C.H.; Landegren, U.; Ten Dijke, P.; et al. Specific interactions between Smad proteins and AP-1 components determine TGFβ-induced breast cancer cell invasion. Oncogene 2013, 32, 3606–3615.
  19. Ishikawa, F.; Miyoshi, H.; Nose, K.; Shibanuma, M. Transcriptional induction of MMP-10 by TGF-beta, mediated by activation of MEF2A and downregulation of class IIa HDACs. Oncogene 2010, 29, 909–919.
  20. Delimont, D.; Dufek, B.M.; Meehan, D.T.; Zallocchi, M.; Gratton, M.A.; Phillips, G.; Cosgrove, D. Laminin alpha2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis. PLoS ONE 2014, 9, e99083.
  21. Huang, X.; Zhu, H.; Gao, Z.; Li, J.; Zhuang, J.; Dong, Y.; Shen, B.; Li, M.; Zhou, H.; Guo, H.; et al. Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p. J. Biol. Chem. 2018, 293, 6693–6706.
  22. Zhou, L.; Chen, X.; Lu, M.; Wu, Q.; Yuan, Q.; Hu, C.; Miao, J.; Zhang, Y.; Li, H.; Hou, F.F.; et al. Wnt/β-catenin links oxidative stress to podocyte injury and proteinuria. Kidney Int. 2019, 95, 830–845.
  23. Tan, R.J.; Zhou, D.; Zhou, L.; Liu, Y. Wnt/β-catenin signaling and kidney fibrosis. Kidney Int. Suppl. 2014, 4, 84–90.
  24. Zhou, D.; Tan, R.J.; Fu, H.; Liu, Y. Wnt/β-catenin signaling in kidney injury and repair: A double-edged sword. Lab. Investig. 2016, 96, 156–167.
  25. Deraz, E.M.; Kudo, Y.; Yoshida, M.; Obayashi, M.; Tsunematsu, T.; Tani, H.; Siriwardena, S.B.; Keikhaee, M.R.; Qi, G.; Iizuka, S.; et al. MMP-10/stromelysin-2 promotes invasion of head and neck cancer. PLoS ONE 2011, 6, e25438.
  26. Saunders, W.B.; Bayless, K.J.; Davis, G.E. MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. J. Cell Sci. 2005, 118, 2325–2340.
  27. Jackson, H.W.; Defamie, V.; Waterhouse, P.; Khokha, R. TIMPs: Versatile extracellular regulators in cancer. Nat. Rev. Cancer 2017, 17, 38–53.
  28. Murphy, G. Tissue inhibitors of metalloproteinases. Genome Biol. 2011, 12, 233.
  29. Batra, J.; Robinson, J.; Soares, A.S.; Fields, A.P.; Radisky, D.C.; Radisky, E.S. Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: Binding studies and crystal structure. J. Biol. Chem. 2012, 287, 15935–15946.
  30. Batra, J.; Soares, A.S.; Mehner, C.; Radisky, E.S. Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes. PLoS ONE 2013, 8, e75836.
  31. Saunders, W.B.; Bohnsack, B.L.; Faske, J.B.; Anthis, N.J.; Bayless, K.J.; Hirschi, K.K.; Davis, G.E. Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J. Cell Biol. 2006, 175, 179–191.
  32. El Ashry, E.S.H.; Awad, L.F.; Teleb, M.; Ibrahim, N.A.; Abu-Serie, M.M.; Abd Al Moaty, M.N. Structure-based design and optimization of pyrimidine- and 1,2,4-triazolopyrimidine-based matrix metalloproteinase-10/13 inhibitors via Dimroth rearrangement towards targeted polypharmacology. Bioorg. Chem. 2020, 96, 103616.
  33. Senn, N.; Ott, M.; Lanz, J.; Riedl, R. Targeted polypharmacology: Discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor. J. Med. Chem. 2017, 60, 9585–9598.
  34. Nam, D.H.; Rodriguez, C.; Remacle, A.G.; Strongin, A.Y.; Ge, X. Active-site MMP-selective antibody inhibitors discovered from convex paratope synthetic libraries. Proc. Natl. Acad. Sci. USA 2016, 113, 14970–14975.
  35. Razai, A.S.; Eckelman, B.P.; Salvesen, G.S. Selective inhibition of matrix metalloproteinase 10 (MMP10) with a single-domain antibody. J. Biol. Chem. 2020, 295, 2464–2472.
  36. Miyata, Y.; Iwata, T.; Maruta, S.; Kanda, S.; Nishikido, M.; Koga, S.; Kanetake, H. Expression of matrix metalloproteinase-10 in renal cell carcinoma and its prognostic role. Eur. Urol. 2007, 52, 791–797.
  37. Zuo, Y.Y.; Wang, C.; Sun, X.L.; Hu, C.X.; Liu, J.X.; Hong, X.; Shen, W.W.; Nie, J.; Hou, F.F.; Zhou, L.L.; et al. Identification of matrix metalloproteinase-10 as a key mediator of podocyte injury and proteinuria. Kidney Int. 2021, 100, 837–849.
  38. Hu, C.; Zuo, Y.; Ren, Q.; Sun, X.; Zhou, S.; Liao, J.; Hong, X.; Miao, J.; Zhou, L.; Liu, Y. Matrix metalloproteinase-10 protects against acute kidney injury by augmenting epidermal growth factor receptor signaling. Cell Death Dis. 2021, 12, 70.
  39. Toni, M.; Hermida, J.; Goni, M.J.; Fernandez, P.; Parks, W.C.; Toledo, E.; Montes, R.; Diez, N. Matrix metalloproteinase-10 plays an active role in microvascular complications in type 1 diabetic patients. Diabetologia 2013, 56, 2743–2752.
  40. Mora-Gutierrez, J.M.; Rodriguez, J.A.; Fernandez-Seara, M.A.; Orbe, J.; Escalada, F.J.; Soler, M.J.; Slon Roblero, M.F.; Riera, M.; Paramo, J.A.; Garcia-Fernandez, N. MMP-10 is increased in early stage diabetic kidney disease and can be reduced by renin-angiotensin system blockade. Sci. Rep. 2020, 10, 26.
  41. Su, M.; Hu, X.; Lin, J.; Zhang, L.; Sun, W.; Zhang, J.; Tian, Y.; Qiu, W. Identification of candidate genes involved in renal ischemia/reperfusion injury. DNA Cell Biol. 2019, 38, 256–262.
  42. Kirita, Y.; Wu, H.; Uchimura, K.; Wilson, P.C.; Humphreys, B.D. Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury. Proc. Natl. Acad. Sci. USA 2020, 117, 15874–15883.
  43. Zhou, D.; Li, Y.; Lin, L.; Zhou, L.; Igarashi, P.; Liu, Y. Tubule-specific ablation of endogenous beta-catenin aggravates acute kidney injury in mice. Kidney Int. 2012, 82, 537–547.
  44. Grgic, I.; Hofmeister, A.F.; Genovese, G.; Bernhardy, A.J.; Sun, H.; Maarouf, O.H.; Bijol, V.; Pollak, M.R.; Humphreys, B.D. Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo. Kidney Int. 2014, 86, 1116–1129.
  45. Naudin, C.; Smith, B.; Bond, D.R.; Dun, M.D.; Scott, R.J.; Ashman, L.K.; Weidenhofer, J.; Roselli, S. Characterization of the early molecular changes in the glomeruli of Cd151 (-/-) mice highlights induction of mindin and MMP-10. Sci. Rep. 2017, 7, 15987.
  46. Gobin, E.; Bagwell, K.; Wagner, J.; Mysona, D.; Sandirasegarane, S.; Smith, N.; Bai, S.; Sharma, A.; Schleifer, R.; She, J.X. A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential. BMC Cancer 2019, 19, 581.
  47. De Peralta-Venturina, M.; Moch, H.; Amin, M.; Tamboli, P.; Hailemariam, S.; Mihatsch, M.; Javidan, J.; Stricker, H.; Ro, J.Y.; Amin, M.B. Sarcomatoid differentiation in renal cell carcinoma: A study of 101 cases. Am. J. Surg. Pathol. 2001, 25, 275–284.
  48. Lin, T.C.; Yeh, Y.M.; Fan, W.L.; Chang, Y.C.; Lin, W.M.; Yang, T.Y.; Hsiao, M. Ghrelin upregulates oncogenic Aurora A to promote renal cell carcinoma invasion. Cancers 2019, 11, 303.
  49. Petrella, B.L.; Vincenti, M.P. Interleukin-1β mediates metalloproteinase-dependent renal cell carcinoma tumor cell invasion through the activation of CCAAT enhancer binding protein β. Cancer Med. 2012, 1, 17–27.
  50. Saini, S.; Liu, J.; Yamamura, S.; Majid, S.; Kawakami, K.; Hirata, H.; Dahiya, R. Functional significance of secreted Frizzled-related protein 1 in metastatic renal cell carcinomas. Cancer Res. 2009, 69, 6815–6822.
  51. Homma, T.; Sakai, M.; Cheng, H.F.; Yasuda, T.; Coffey, R.J., Jr.; Harris, R.C. Induction of heparin-binding epidermal growth factor-like growth factor mRNA in rat kidney after acute injury. J. Clin. Investig. 1995, 96, 1018–1025.
  52. Zhuang, S.; Kinsey, G.R.; Rasbach, K.; Schnellmann, R.G. Heparin-binding epidermal growth factor and Src family kinases in proliferation of renal epithelial cells. Am. J. Physiol. Renal Physiol. 2008, 294, F459–F468.
  53. He, S.; Liu, N.; Bayliss, G.; Zhuang, S. EGFR activity is required for renal tubular cell dedifferentiation and proliferation in a murine model of folic acid-induced acute kidney injury. Am. J. Physiol. Renal Physiol. 2013, 304, F356–F366.
  54. Chen, J.; Chen, J.K.; Harris, R.C. Deletion of the epidermal growth factor receptor in renal proximal tubule epithelial cells delays recovery from acute kidney injury. Kidney Int. 2012, 82, 45–52.
  55. Chen, J.; You, H.; Li, Y.; Xu, Y.; He, Q.; Harris, R.C. EGF receptor-dependent YAP activation is important for renal recovery from AKI. J. Am. Soc. Nephrol. 2018, 29, 2372–2385.
  56. Yamamoto, Y.; Iyoda, M.; Tachibana, S.; Matsumoto, K.; Wada, Y.; Suzuki, T.; Iseri, K.; Saito, T.; Fukuda-Hihara, K.; Shibata, T. Erlotinib attenuates the progression of chronic kidney disease in rats with remnant kidney. Nephrol. Dial. Transplant. 2018, 33, 598–606.
  57. Tang, J.; Liu, N.; Zhuang, S. Role of epidermal growth factor receptor in acute and chronic kidney injury. Kidney Int. 2013, 83, 804–810.
  58. Harskamp, L.R.; Gansevoort, R.T.; van Goor, H.; Meijer, E. The epidermal growth factor receptor pathway in chronic kidney diseases. Nat. Rev. Nephrol. 2016, 12, 496–506.
  59. Li, Z.; Li, Y.; Overstreet, J.M.; Chung, S.; Niu, A.; Fan, X.; Wang, S.; Wang, Y.; Zhang, M.Z.; Harris, R.C. Inhibition of Epidermal Growth Factor Receptor Activation Is Associated with Improved Diabetic Nephropathy and Insulin Resistance in Type 2 Diabetes. Diabetes 2018, 67, 1847–1857.
  60. Mulder, G.M.; Nijboer, W.N.; Seelen, M.A.; Sandovici, M.; Bos, E.M.; Melenhorst, W.B.; Trzpis, M.; Kloosterhuis, N.J.; Visser, L.; Henning, R.H.; et al. Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury. J. Pathol. 2010, 221, 183–192.
  61. Kefaloyianni, E.; Keerthi Raja, M.R.; Schumacher, J.; Muthu, M.L.; Krishnadoss, V.; Waikar, S.S.; Herrlich, A. Proximal tubule-derived amphiregulin amplifies and integrates profibrotic EGF receptor signals in kidney fibrosis. J. Am. Soc. Nephrol. 2019, 30, 2370–2383.
  62. Liu, N.; Guo, J.K.; Pang, M.; Tolbert, E.; Ponnusamy, M.; Gong, R.; Bayliss, G.; Dworkin, L.D.; Yan, H.; Zhuang, S. Genetic or pharmacologic blockade of EGFR inhibits renal fibrosis. J. Am. Soc. Nephrol. 2012, 23, 854–867.
  63. Overstreet, J.M.; Wang, Y.; Wang, X.; Niu, A.; Gewin, L.S.; Yao, B.; Harris, R.C.; Zhang, M.Z. Selective activation of epidermal growth factor receptor in renal proximal tubule induces tubulointerstitial fibrosis. FASEB J. 2017, 31, 4407–4421.
  64. Xu, L.; Li, X.; Zhang, F.; Wu, L.; Dong, Z.; Zhang, D. EGFR drives the progression of AKI to CKD through HIPK2 overexpression. Theranostics 2019, 9, 2712–2726.
  65. Carrasco-Rando, M.; Prieto-Sanchez, S.; Culi, J.; Tutor, A.S.; Ruiz-Gomez, M. A specific isoform of Pyd/ZO-1 mediates junctional remodeling and formation of slit diaphragms. J. Cell Biol. 2019, 218, 2294–2308.
  66. Itoh, M.; Nakadate, K.; Matsusaka, T.; Hunziker, W.; Sugimoto, H. Effects of the differential expression of ZO-1 and ZO-2 on podocyte structure and function. Genes Cells 2018, 23, 546–556.
  67. Wang, C.; Liu, J.; Zhang, X.; Chen, Q.; Bai, X.; Hong, X.; Zhou, L.; Liu, Y. Role of miRNA-671-5p in mediating Wnt/β-catenin-triggered podocyte injury. Front. Pharmacol. 2022, 12, 784489.
  68. Sagar, A.; Arif, E.; Solanki, A.K.; Srivastava, P.; Janech, M.G.; Kim, S.H.; Lipschutz, J.H.; Ashish, S.-H.K.; Nihalani, D. Targeting Neph1 and ZO-1 protein-protein interaction in podocytes prevents podocyte injury and preserves glomerular filtration function. Sci. Rep. 2017, 7, 12047.
  69. Itoh, M.; Nakadate, K.; Horibata, Y.; Matsusaka, T.; Xu, J.; Hunziker, W.; Sugimoto, H. The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1. PLoS ONE 2014, 9, e106621.
  70. Balda, M.S.; Matter, K. The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J. 2000, 19, 2024–2033.
  71. Kim, S.; Kim, G.H. Roles of claudin-2, ZO-1 and occludin in leaky HK-2 cells. PLoS ONE 2017, 12, e0189221.
  72. Amoozadeh, Y.; Anwer, S.; Dan, Q.; Venugopal, S.; Shi, Y.; Branchard, E.; Liedtke, E.; Ailenberg, M.; Rotstein, O.D.; Kapus, A.; et al. Cell confluence regulates claudin-2 expression: Possible role for ZO-1 and Rac. Am. J. Physiol. Cell Physiol. 2018, 314, C366–C378.
  73. Festa, B.P.; Chen, Z.; Berquez, M.; Debaix, H.; Tokonami, N.; Prange, J.A.; Hoek, G.V.; Alessio, C.; Raimondi, A.; Nevo, N.; et al. Impaired autophagy bridges lysosomal storage disease and epithelial dysfunction in the kidney. Nat. Commun. 2018, 9, 161.
  74. Balda, M.S.; Garrett, M.D.; Matter, K. The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density. J. Cell Biol. 2003, 160, 423–432.
  75. He, L.; Zhou, Z.; Shao, Y.; Yang, Z.; Zhou, S.; Zou, X.; Zhou, Y.; Tan, G. Bradykinin potentially stimulates cell proliferation in rabbit corneal endothelial cells through the ZO1/ZONAB pathway. Int. J. Mol. Med. 2018, 42, 71–80.
  76. Ruan, Y.C.; Wang, Y.; Da Silva, N.; Kim, B.; Diao, R.Y.; Hill, E.; Brown, D.; Chan, H.C.; Breton, S. CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway. J. Cell Sci. 2014, 127, 4396–4408.
  77. Xu, X.; Zhang, X.; Gao, L.; Liu, C.; You, K. Neonatal hyperoxia downregulates claudin-4, occludin, and ZO-1 expression in rat kidney accompanied by impaired proximal tubular development. Oxid. Med. Cell Longev. 2020, 2020, 2641461.
  78. Gonzalez-Mariscal, L.; Namorado, M.C.; Martin, D.; Luna, J.; Alarcon, L.; Islas, S.; Valencia, L.; Muriel, P.; Ponce, L.; Reyes, J.L. Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules. Kidney Int. 2000, 57, 2386–2402.
  79. Lima, W.R.; Parreira, K.S.; Devuyst, O.; Caplanusi, A.; N’Kuli, F.; Marien, B.; Van Der Smissen, P.; Alves, P.M.; Verroust, P.; Christensen, E.I.; et al. ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells. J. Am. Soc. Nephrol. 2010, 21, 478–488.
  80. Nie, M.; Balda, M.S.; Matter, K. Stress- and Rho-activated ZO-1-associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival. Proc. Natl. Acad. Sci. USA 2012, 109, 10897–10902.
  81. Kitada, K.; Nakano, D.; Ohsaki, H.; Hitomi, H.; Minamino, T.; Yatabe, J.; Felder, R.A.; Mori, H.; Masaki, T.; Kobori, H.; et al. Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J. Diabetes Complicat. 2014, 28, 604–611.
  82. Raggi, C.; Luciani, A.; Nevo, N.; Antignac, C.; Terryn, S.; Devuyst, O. Dedifferentiation and aberrations of the endolysosomal compartment characterize the early stage of nephropathic cystinosis. Hum. Mol. Genet. 2014, 23, 2266–2278.
  83. Schlage, P.; Kockmann, T.; Sabino, F.; Kizhakkedathu, J.N.; Auf dem Keller, U. Matrix metalloproteinase 10 degradomics in keratinocytes and epidermal tissue identifies bioactive substrates with pleiotropic functions. Mol. Cell Proteom. 2015, 14, 3234–3246.
  84. Barksby, H.E.; Milner, J.M.; Patterson, A.M.; Peake, N.J.; Hui, W.; Robson, T.; Lakey, R.; Middleton, J.; Cawston, T.E.; Richards, C.D.; et al. Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation: Implications for cartilage degradation in arthritis. Arthritis Rheum. 2006, 54, 3244–3253.
  85. Schlage, P.; Egli, F.E.; Nanni, P.; Wang, L.W.; Kizhakkedathu, J.N.; Apte, S.S.; Auf dem Keller, U. Time-resolved analysis of the matrix metalloproteinase 10 substrate degradome. Mol. Cell. Proteom. 2014, 13, 580–593.
  86. Yazgan, B.; Avci, F.; Memi, G.; Tastekin, E. Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin. Exp. Biol. Med. 2021, 246, 1917–1927.
  87. Wozniak, J.; Floege, J.; Ostendorf, T.; Ludwig, A. Key metalloproteinase-mediated pathways in the kidney. Nat. Rev. Nephrol. 2021, 17, 513–527.
  88. Liu, Z.; Tan, R.J.; Liu, Y. The many faces of matrix metalloproteinase-7 in kidney diseases. Biomolecules 2020, 10, 960.
  89. Djuric, T.; Zivkovic, M.; Milosevic, B.; Andjelevski, M.; Cvetkovic, M.; Kostic, M.; Stankovic, A. MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract. Pediatr. Nephrol. 2014, 29, 879–884.
  90. Contreras-Salinas, H.; Meza-Rios, A.; Garcia-Banuelos, J.; Sandoval-Rodriguez, A.; Sanchez-Orozco, L.; Garcia-Benavides, L.; De la Rosa-Bibiano, R.; Monroy Ramirez, H.C.; Gutierrez-Cuevas, J.; Santos-Garcia, A.; et al. Fibrosis regression is induced by AdhMMP8 in a murine model of chronic kidney injury. PLoS ONE 2020, 15, e0243307.
  91. Ren, J.; Zhang, J.; Rudemiller, N.P.; Griffiths, R.; Wen, Y.; Lu, X.; Privratsky, J.R.; Gunn, M.D.; Crowley, S.D. Twist1 in infiltrating macrophages attenuates kidney fibrosis via matrix metallopeptidase 13-mediated matrix degradation. J. Am. Soc. Nephrol. 2019, 30, 1674–1685.
  92. Chen, L.; Cao, G.; Wang, M.; Feng, Y.L.; Chen, D.Q.; Vaziri, N.D.; Zhuang, S.; Zhao, Y.Y. The matrix metalloproteinase-13 inhibitor poricoic acid ZI ameliorates renal fibrosis by mitigating epithelial-mesenchymal transition. Mol. Nutr. Food Res. 2019, 63, e1900132.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Academic Video Service
Feedback