Role of defensins in diabetic wound healing

Table 1 Defensins play multiple roles in different diseases

Defensin		Main cellular source	Action
α-defensin	HNP1	Neutrophils; monocytes; macrophages; natural killer cells	Increase the healing rate of MRSA-infected wounds[6]; promote hemostasis[7]; r/affect the cardiovascular system[8]; inhibit thrombus formation[9]	Anti-infection and immunoregulation[23]
	HNP2-3		Anti-tumor activity[10]
	HNP4	Neutrophils	Characterize benign and malignant salivary gland tumors[11]
	HD5-6	Intestinal Paneth cells	Reverse dyslipidemia and improve glucoregulatory capacity[12]; anti-tumor ability[13]; amyloid inhibitor[14]
β-defensin	HBD1	Epithelial cells; monocytes; macrophages	Anti-tumor activity[15]; potentiate osteoclastogenesis[16]	Induce the secretion of angiogenin[54]; anti-infection and immunoregulation[23]
	HBD2		Accelerate wound healing[17]; Oncolytic activity[18]; reduce alcoholic liver injury[19]
	HBD3		Accelerate wound healing[20]; induce IL-8 release and apoptosis in airway smooth muscle cells[21]
	HBD4	Epithelial cells	Stimulate/suppress cancer cell proliferation and viability[22]

HNP: Human neutrophil peptide; HBD: Human β-defensins.

Table 2 Defensins play a potential role in wound healing

Stage	Defensin	Activation
Inflammation	HNP1-2, HBD1-3[28]	Recruitment of leukocytes
	HNP1-4[29]	Secretion of inflammatory cytokines like IL-8
	HBD2-4[32]	Activation of the p38 and ERK1/2 MAPK pathways
	HNP1, HBD2[35]	Activation of the p42/44 MAPK pathways
	HBD2, HBD3[36]	Down-regulate the TIR, TRAF-6, NF-κB of TLR signaling pathways
	HBD3[37]	Induce M2 macrophage differentiation
Re-epithelialization	HNP1[43], HBD2-3[42]	Induce keratinocyte migration and proliferation
	HBD1[44]	Protect keratinocytes from apoptosis
Collagen synthesis	HNP1[45]	Enhance extracellular matrix deposition
	HBD3[20,37]	Increase the expression of MMP-2, and down-regulate the expression of MMP-9
Fibroplasia	HNP1[45], HBD2[46]	Promote the proliferation and activation of fibroblasts
Angiogenesis	HNP1[51], HBD2[52], HBD3[53]	Induce VEGF
	HBD1-4[54]	Induce angiogenin
	HNPs[55]	Inhibit adhesion and migration of endothelial cell
Nerve reconstruction	HNP1[40]	Promote the recovery of neurological function
	HBD3[57]	Modulate the expression of nerve elongation factors
Antimicrobial activity	HNP1-4, HBD1-4[61]	Exhibit a broad range of antimicrobial properties
	HBD2[60]	Reduce biofilm formation
	HNP1-3[62]	Neutralize bacterial toxins
	HNP1, HBD1, HBD3[63]	Show synergy of action with antibiotics

HNP: Human neutrophil peptide; HBD: Human β-defensins; MMP: Matrix metalloproteinase.