Table 3.
Matricellular proteins regulating wound healing (re-epithelialization), epidermal stem cells, and aging skin.
| Process | Matricellular Protein |
Function | References & Study Model |
|---|---|---|---|
| Wound healing (Re-epithelialization) |
CCN1 | upregulated during skin repair, induces myofibroblast senescence to minimize fibrosis, enhances neutrophil efferocytosis by macrophages for resolution of inflammation | [147,148] (summary), [149,150] (mouse) |
| promotes keratinocytes proliferation and induces EMT during skin expansion | [151] (human primary keratinocytes & in vivo mouse), [152] (human & rat skin) | ||
| Thrombospondin 1 | spatiotemporal expression regulates wound healing processes | [153,154] (mouse) | |
| promotes keratinocyte migration and proliferation | [71] (human keratinocytes culture & in vivo mouse), [155] (mouse) | ||
| Thrombospondin 2 | influences vascularization but not re-epithelialization | [153,156] (mouse) | |
| Thrombospondin 4 | accelerates wound healing through increased keratinocytes proliferation and fibroblasts migration | [157] (human & mouse skin) | |
| Thrombospondin 5 | suppresses keratinocyte activation | [65] (human skin) | |
| Periostin | regulates re-epithelialization and wound contraction, downregulated in aging skin | [108,158,159] (mouse), [43] (human skin) | |
| R-spondin 1 | regulates skin differentiation and malignancy, promotes wound healing and re-epithelialization | [160] (human & mouse), [161] (rat) | |
| TGFBI | BM component, promotes epidermal stem cell proliferation and re-epithelialization | [162] (human & mouse) | |
| Aging | Fibulin 7 | decreased in aged BM, maintains epidermal stem cell heterogeneity, binds to periostin and tenascin C and improves re-epithelialization in aging skin wound healing | [18] (mouse) |
| Thrombospondin 1 | upregulated in epidermal stem cells and dermal fibroblasts during aging and may contribute to aging-associated vasculature changes | [124,163] (mouse), [164] (human dermal fibroblasts) | |
| Mindin (Spon2) | Mindin promotes epidermal stem/progenitor cell expansion downstream of Snail, inhibition of Mindin and fibulin 5 rescues Snail-induced skin fibrosis | [165,166,167] (mouse) | |
| Fibulin 5 | [168] (mouse) | ||
| CCN1 | promotes fibroblast senescence in skin dermis | [149,169] (mouse) | |
| CCN2 | decreased in aging dermis is associated with collagen loss | [170] (human skin & dermal fibroblasts), [171] (human dermal fibroblasts) |