Therapeutic role of growth factors in treating diabetic wound

Table 1 Main growth factors in wound healing

Type of GF	Source cells	Target cells	Receptor⁄signaling protein	Involved wound healing process	Acute wound	Chronic wound	Ref.
VEGF	Keratinocytes, fibroblasts, macrophages, endothelial cells	Endothelial cells, macrophages	ICAM-1, VCAM-1, PLCγ/PKC/Ras/Raf/MEK/ERK	Inflammation, angiogenesis	Increased	Decreased	[151-158]
TGF-β	Fibroblasts, keratinocytes, macrophages, platelets	Fibroblasts, keratinocytes, macrophages, leukocytes, endothelial cells	TGF-βRI-II, Smad 2-4, α-SMA, MAPK, integrins	Inflammation, angiogenesis, granulation tissue formation, collagen synthesis, matrix formation and remodeling, leukocyte chemotactic function	Increased	Decreased	[157,159-174]
PDGF	Platelets	Leukocytes, macrophages, fibroblasts	PDGFR, Ras/Erk1/2/MAPK, PI3K	Inflammation, re-epithelialization, collagen deposition, tissue remodelling	Increased	Decreased	[108,157,175,176]
HGF	Fibroblasts	Endothelial cells, keratinocytes	c-Met, ERK1/2, Akt, PAK-1/2, Gab1	Suppression of inflammation, granulation tissue formation, angiogenesis, re-epithelialization	-	-	[155,176-180]
bFGF	Keratinocytes, fibroblasts, endothelial cells	Keratinocytes, fibroblasts, endothelial cells	ERK2	Angiogenesis, granulation tissue formation	Increased	Decreased	[108,175,181-184]
FGF-7, FGF-10	Fibroblasts, keratinocytes	Keratinocytes	Peroxiredoxin-6, Nrf2, Nrf3	Re-epithelialization, detoxification of ROS	-	-	[185-188]
EGF, HB-EGF, TGF-α	Platelets, macrophages, keratinocytes	Fibroblasts, endothelial cells, keratinocytes	EGFR, STAT3, AP1, PI3K, ERK	Tissue formation, re-epithelialization	Increased	Decreased	[189-197]

ICAM-1: Intercellular adhesion molecule 1; VCAM-1: Vascular cell adhesion molecule 1; PLC: Phospholipase C; PKC: Protein kinase C; α-SMA: α smooth muscle actin; MAPK: Mitogen-activated protein kinase; PI3K: Phosphoinositide 3-kinase; VEGF: Vascular endothelial growth factor; PDGF: Platelet-derived growth factor; EGF: Epidermal growth factor; FGF: Fibroblast growth factor; HGF: Hepatocyte growth factor; HB-EGF: heparin-binding epidermal growth factor.