Table 1.
The important genes during different phases of wound healing and scar formation
| Gene/factor | Role in | Effects | References | |
|---|---|---|---|---|
| IL-8 | Induction Inhibition | Inflammation; recruitment of immune cells and fibroblasts; hemostasis of epidermis; proliferation of keratinocytes; production of MMP-9 in keratinocytes; angiogenesis − |
Pro-fibrotic | [33–35] |
|
| ||||
| IL-1α | Induction Inhibition | Inflammation; activity of keratinocytes, fibroblasts, and endothelial cells; deposition of collagen Restoration of the skin architecture |
Pro-fibrotic | [37,38] |
|
| ||||
| IL-1β | Induction Inhibition | Expression of decorin; activity and homing of PBMC; function of CXCR4-CXCL 12 axis; proliferation of fibroblasts Restoration of the skin architecture | Pro-fibrotic | [37, 39] |
|
| ||||
| IL-6 | Induction Inhibition | The pro-inflammatory function of immune cells; timely resolution of wound healing − |
Pro-fibrotic | [41] |
|
| ||||
| TNF-α | Induction Inhibition | Inflammation; EMT; expression of MMPs; apoptosis TGF-β and CTGF signaling; expression of αSMA − |
Pro-fibrotic or anti-fibrotic | [42–45, 95] |
|
| ||||
| IL-10 | Induction Inhibition | Physiological wound healing; organization and maturation of ECM; production of hyaluronic; angiogenesis Activation and migration of immune cell; expression of TGF-β; deposition of excessive collagen; expression of αSMA | Anti-fibrotic | [46–49] |
|
| ||||
| PDGF | Induction Inhibition | Chemotaxis of dermal fibroblasts; proliferation of keratinocyte and fibroblast; synthesis of ECM components; degradation of the old collagen fibers; angiogenesis − |
Pro-fibrotic | [51–54] |
|
| ||||
| IGF-1 | Induction Inhibition | The proliferation of fibroblast; synthesis and organization of ECM; renewal activity of keratinocytes; angiogenesis; wound contracture Apoptosis of keratinocytes | Pro-fibrotic | [55,59] |
|
| ||||
| TGF-β1;TGF-β2 | Induction Inhibition | Migration of inflammatory cells, keratinocyte, and fibroblasts; proliferation of cells; expression and organization of ECM; expression of TIMPs and αSMA; angiogenesis; trans-differentiation of fibroblasts Expression of MMPs; apoptosis | Pro-fibrotic | [34, 61, 62, 68] |
|
| ||||
| TGF-β3 | Induction Inhibition | Expression of MMPs; degradation of collagen fibers Differentiation of fibroblasts; deposition of collagen type 1 | Anti-fibrotic | [34, 62, 68] |
|
| ||||
| P311 | Induction Inhibition | Translation of TGF-β isoforms; proliferation and migration of cells; expression of COL1A1 and αSMA; tensile strength of newly formed tissue and normal scar formation − |
Pro-fibrotic | [69, 70] |
|
| ||||
| VEGF | Induction Inhibition | Recruitment of mast cells and other inflammatory cells; proliferation and migration of endothelial cells and keratinocytes; angiogenesis − |
Pro-fibrotic | [71, 74] |
|
| ||||
| Hox-A9 | Induction Inhibition | Transcription of VEGF − |
Pro-fibrotic | [72] |
|
| ||||
| Hox-A5 | Induction Inhibition | Expression of antiangiogenic genes Expression of pro-angiogenic genes | Anti-fibrotic | [72] |
|
| ||||
| p53; Bax | Induction Inhibition | Programmed cell death; organization of collagen − |
Anti-fibrotic | [77] |
|
| ||||
| Snail-2; SFRP2 | Induction Inhibition | Synthesis of collagen Programmed cell death; organization of collagen |
Pro-fibrotic | [76] |
|
| ||||
| MMP-1 (collagenases I) |
Induction Inhibition | Migration and reepithelialization of keratinocyte; degradation of fibrillar collagens − |
Anti-fibrotic | [78, 80] |
|
| ||||
| MMP-2 (gelatinases) | Induction Inhibition | Degeneration of gelatin segments and other ECM proteins; prolonged remodeling events − |
Pro-fibrotic or anti-fibrotic | [79, 80, 86] |
|
| ||||
| MMP-3 | Induction Inhibition | Degradation of collagen type III; wound contraction by fibroblasts − |
Anti-fibrotic | [78, 80] |
|
| ||||
| MMP-8 (collagenases II) |
Induction Inhibition | Degradation of fibrillar collagens − |
Anti-fibrotic | [78, 80] |
|
| ||||
| MMP-9 (gelatinases) | Induction Inhibition | Migration and reepithelialization of keratinocytes; degeneration of gelatin segments and other ECM proteins; early events of wound repair | Anti-fibrotic | [78–80] |
|
| ||||
| MMP-13 (collagenases III) | Induction Inhibition | Degradation of fibrillar collagens | Anti-fibrotic | [78, 80] |
|
| ||||
| TIMP-1 | Induction Inhibition | Proliferation of keratinocytes Degradation of ECM; activity of MMP-1 and −2; apoptosis |
Pro-fibrotic | [80, 81, 83] |
|
| ||||
| TIMP-2 | Induction Inhibition | Migration of keratinocytes Degradation of ECM; activity of MMP-1 and −2; apoptosis |
Pro-fibrotic | [81, 82] |
|
| ||||
| TIMP-3 | Induction Inhibition | − Degradation of ECM; activity of MMP-1, −2, −3, −9, −13; inflammation; angiogenesis |
Pro-fibrotic | [80, 81] |
|
| ||||
| PLOD2 | Induction Inhibition | Pyridinoline cross-linkage of collagen; accumulation of collagen Degradation of collagen | Pro-fibrotic | [87, 88] |
|
| ||||
| Decorin | Induction Inhibition | Reorganization of collagen fibers; tensile strength of the skin TGF-β signaling | Anti-fibrotic | [6, 61, 89] |
SFRP2, secreted frizzled-related protein 2.