Table 1.

Various mechanisms related to dysfunctional keratinocytes in diabetic wound healing.

Dysfunction	Mechanism	Ref.
Increased oxidative stress and ROS	Impaired antioxidant ability results in mitochondria damage	[52]
Abnormal expression of MMPs	Decreased mRNA level and activity of MMP-2 and MMP-9 and increased TIMP-1	[57]
	Decreased expression of MMP-1 and α2β1 integrin	[58]
	Decreased expression of IL-22 may suppress production of MMP-3 in keratinocytes	[59]
Impaired proliferation and migration of KCs	Decreased expression of phosphorylated p125FAK	[57]
	Increased AGEs	[61]
	Increased O-GlcNAc glycosylation and decreased expression of Gal-7	[62]
	Downregulated the p38/MAPK pathway followed by inactivation of autophagy	[76]
	Increased percentage of M1 macrophage infiltration followed by increased secretion of TNF-α, which upregulates TIMP1 expression	[77]
	Increased expression of FOXO1 stimulates the expression of MMP-9	[7]
	Impaired expression of K16	[58]
	Increased expression of suppressor of cytokine signaling-3 (SOCS-3)	[85]
	Increased expression of Connexin 43	[86]
	Increased keratinocyte resistance to acetylcholine (Ach)	[91]
Chronic inflammation	Increased neutrophil and macrophage infiltration	[49]
	Increased pro-inflammatory cytokines (IL-1, IL-6, IL-8 and TNF-α)	[93]
	Activation of the TNF-α and TLR4 signaling pathway	[95]
	Decreased expression of Wnt family member 7A (wnt7a)	[97]
	Increased expression of MIP-2 and MCP1	[92]
	Decreased COX-1 expression and increased COX-2 expression	[98]
Chronic infection	Reduced diversity of microbiota and promoted biofilm formation	[48]
	Bacteria directly influenced keratinocytes (increasing apoptosis, diminishing keratinocyte migration and proliferation)	[103]
	Decreasing mRNA and protein levels of human β-defensins-2 (HBD-2) and HBD-3	[104]
	Decreased expression of mRNA and protein of cathelicidin	[107]
Impaired angiogenesis	Impaired the recruitment and migration of endothelial cells and EPCs	[112]
	Increased the expression of Thrombospondin-1 (TSP-1)	[114]
	Decreased the expression of vascular endothelial growth factor (VEGF)	[116]