... Stimulation of angiogenesis, VEGF expression; control of endothelial cells migration, fibroblast growth and collagen synthesis; recruitment of MSCs [61][62][63][64][65] constitutive presence in intact skin [66] eAGR2 induces lactate production, glucose uptake and HIF-1α expression; eAGR2 expression is upregulated by HIF-1α [15,67,68] VEGF Stimulation of angiogenesis, activation of endothelial cells, proteolytic enzymes secretion, releasing of MMPs for further proliferation and migration [69,70] lower levels [71] eAGR2 enhances VEGF homodimerization, thus controlling angiogenesis, endothelial cells and fibroblasts invasion [45,72] FGFs control cell proliferation, differentiation and migration; FGF 1, 2, 5, 7, 10 upregulation during cutaneous WH; in scarless WH FGF signaling downregulates; FGF2 expression increases under the hypoxia [51,64,65,73,74] constitutive presence in intact skin as morphogens; FGF7 and FGF10 downregulate in fetal scarless wounds; FGF2 expression decrease in both scarless and scarring fetal wounds [73,74] eAGR2 enhances FGF2 homodimerization, thus controlling angiogenesis, endothelial cells and fibroblasts invasion [45] MMPs Regulation of matrix stiffness, lysing surrounding tissues, control of ECM remodeling [70,75] no significant differences were found nAG activates MMP, increase collagen degradation [76,77] Collagen I, III collagen III (proliferation phase)-thin fibrils, part of the provisional matrix replaced by the collagen I, orientating along the epidermal surface; low ratio of type III (10%) to type I (20%) collagen [78,79] higher ratio of collagen III (60%) to collagen I (30%) [79] nAG suppresses collagen I and III synthesis, increases collagen degradation [76,77] Cell capabilities keratinocytes-proliferation, migration along the fibrin of the blood clot, closure of the wound surface [7,[80][81][82]; fibroblasts-recruitment to the wound bed, transformation to myofibroblast, secretion ECM [52,55,75,83]; M1-macrophages migration, secrete pro-inflammatory mediators, switch to M2 form [84]; M2-macrophages secrete TGF-β1, PDGF [85][86][87] lower number of M1, M2-macrophages, higher ratio of M2-macrophages to M1, reduced presentation time [88] eAGR2 accelerates fibroblasts and keratinocytes migration; eAGR2 promotes epithelial morphogenesis, disrupts cell-cell contact and basal laminin; iAGR2 prevents EMT induction [24,[89][90][91][92][93] In certain tumor systems, both TGF-β and TNF-α have been shown to inhibit eAGR2 expression ( Figure 3A) [56]. ...