The ECM is mainly composed of various macromolecular substances that constitute a complex network of cellular physiological activities ^[1][15]. Recent studies have shown that ECM plays an increasing role in tissue damage and regeneration, especially in angiogenesis, by providing important cues for cellular responses ^[2][3][16,17]. Tenascins are multifunctional glycoproteins found in the ECM of chordate animals. Studies have validated that tenascin-C, -R, -X, and -W are the four isoforms of the tenascin family, and have similar functions in regulating cell adhesion and cellular responses to injury repair ^{[4][5][6][7][8]}[18,19,20,21,22].

Since it was first discovered in the 1980s, TNC has been the most studied and most representative member of the tenascin family ^[9][10][5,23]. The unique structure of TNC often exists in the form of hexamers, with a molecular weight of approximately 220–400 kDa ^[11][24]. TNC consists of four distinct domains, from N-terminal to C-terminal: the coil-like tenascin assembly (TA) domain; 14.5 epidermal growth factor-like (EGF-L) domain; 17 fibronectin type III (FN III)-like domains; and a fibrinogen-like globule (FBG) domain (Figure 1A). This multi-modular structure enables tenascin to interact with a large number of highly diverse ligands, such as FNIII-like domains that bind different proteins, such as annexin II, syndecan-4, and integrins αvβ3 and α7β1 through alternative splicing ^[12][13][14][25,26,27]. In addition, FNIII-like domains bind to a variety of growth factors, including the vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and transforming growth factor-β (TGF-β). The interactions allow TNC to promote cell migration, cell adhesion, matrix aggregation, protease, and proinflammatory factor synthesis. Therefore, given the structural, expression, and functional characteristics of TNC, the alternative spliceosome of TNC plays different roles in various injuries (Figure 1B) ^{[15][16][17][18][19][20]}[28,29,30,31,32,33].

In adults, the expression of TNC is strictly regulated by cell type and the tissue microenvironment. TNC is nearly undetectable in normal adults, with the exception of embryonic development and a few connective tissues. TNC mainly exists around motor cells, especially in the central nervous system and bone joint system ^[21][34]. TNC plays a role in regulating cell adhesion, motility, and tissue remodeling and is closely related to inflammatory signaling, through which angiogenesis can be achieved. Changes in TNC expression caused by external stimuli cause angiogenesis and are involved in the processes of trauma, tumor, and degeneration. Whereas in the pathological state, TNC exists around the injury, the tumor matrix, and the site of regeneration ^[22][23][35,36].

Injury defined by damage to normal tissues is caused by multiple factors ^[24][37]. The integrity of the tissue is destroyed, along with the loss of a certain amount of normal tissue ^[25][38]. In the wound healing process, there are four relatively distinct phases that include hemostasis, inflammation, proliferation, and remodeling. The first step is the hemostasis phase of wound healing, which entails clotting of blood mediated by platelets ^[26][39]. Angiogenesis is a complex and dynamic process that plays an important role at each stage of wound healing by transforming vascular precursor cells into new blood vessels ^[27][40]. The generation of new capillary beds through angiogenesis is essential for normal healing ^[28][41]. Tissue vascular networks after injury usually involve angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is the process of growing new blood vessels from existing vasculature. Arteriogenesis is the process by which arteries remodel ^[29][30][42,43].

The ECM, including collagen, TNC, matrix metalloproteinases (MMPs), etc., are major players in tissue injury and regeneration, providing important regulatory clues for the formation of new capillaries ^[31][32][44,45]. Usually, angiogenesis increases greatly in the early stage of injury and will increase to 2–3 or even 10 times after injury ^[33][34][46,47]. In the later stages of repair, cell death and vascular degeneration return to normal levels to maintain homeostasis ^[35][48]. TNC is an important component of the ECM and is mainly expressed during tissue repair and tumor growth. The expression level of TNC is dynamically consistent with the changes in angiogenesis after injury in both time and space ^[35][48] (Figure 2). Studies suggested that the physiological repair of tissue injury can be mediated by regulating the dynamic expression of TNC.