Abstract: BACKGROUND: This study provided insight into the molecular mechanisms by which exogenous basic fibroblast growth factor (bFGF) promotes wound healing.
OBJECTIVE: To investigate the effect of exogenous bFGF on macrophage phenotype transition and granulation regeneration during wound repair in rats. 
METHODS: (1) In vitro experiment: Cells were divided into normal control group, low-dose bFGF group, high-dose bFGF group, and bFGF+valproic acid group. 100 and 200 μg/L bFGF was added into the cell culture medium of low-dose bFGF group and high-dose bFGF group, respectively, while 200 μg/L bFGF and 20 mmol/L valproic acid were added into the cell culture medium of valproic acid group. EdU test, scratch test and tubule formation test were used to detect the effects of bFGF on proliferation, migration and angiogenesis of human umbilical vein endothelial cells. (2) In vivo experiment: Sprague-Dawley rats were randomly divided into model group, low-dose bFGF group, high-dose bFGF group and bFGF+valproic acid group. The open wound model of full-thickness skin defect was established in low-dose bFGF group, high-dose bFGF group and bFGF+valproic acid group. Rats in the low- and high-dose bFGF groups were given 100 and 200 μg/L bFGF through subcutaneous injection, while those in the bFGF+valproic acid group received subcutaneous injection of 200 μg/L bFGF and intraperitoneal injection of 10 mg/kg valproic acid. The wound healing rate of rats was detected at 7 and 14 days of administration. TUNEL was used to detect the apoptosis of cells in wound tissue. Enzyme linked immunosorbent assay was used to detect the serum levels of malondialdehyde, superoxide dismutase, tumor necrosis factor-α and interleukin-10. Immunofluorescence detection was conducted to detect the phenotypic transformation of macrophages in wound tissue. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen, platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor in wound tissue. Western blot was used to detect the expression of Notch1 and Jagged1 in wound tissue. 
RESULTS AND CONCLUSION: (1) Compared with the normal control group, bFGF could significantly promote the proliferation, migration and angiogenesis of human umbilical vein endothelial cells in a dose-dependent manner. (2) Compared with the model group, bFGF could significantly promote wound healing, downregulate the rate of apoptosis in wound tissue, decrease the levels of malondialdehyde and tumor necrosis factor-α in serum, increase the levels of superoxide dismutase and interleukin-10, promote the conversion of macrophages to type M2 in wound tissue, upregulate the expression of proliferating cell nuclear antigen, CD31 and vascular endothelial growth factor in wound tissue, and inhibit the expression of Notch1 and Jagged1 in a dose-dependent manner. Valproic acid could partially reverse the promoting effect of bFGF on wound healing. To conclude, bFGF can significantly promote wound healing and granulation regeneration and induce the conversion of macrophages to M2, which may be related to the regulation of Notch1/Jagged1 signaling pathway.

Key words: basic fibroblast growth factor, full-thickness skin defect, wound, macrophage phenotype transition, granulation regeneration, Notch1, Jagged1