Effect of CD137-CD137 ligand pathway on phenotypic transformation of macrophages on wound healing of diabetic foot ulcer
10.3969/j.issn.1006-6187.2025.08.010
- VernacularTitle:CD137-CD137配体通路调控巨噬细胞表型转化影响糖尿病足溃疡创面愈合的研究
- Author:
Heng LI
1
;
Cuilan ZHANG
;
Yuze DUAN
Author Information
1. 571700 儋州,海南西部中心医院内分泌科
- Publication Type:Journal Article
- Keywords:
Diabetic foot ulcer;
CD137-CD137 ligand pathway;
Wound healing;
Macrophage;
Inflammatory factor
- From:
Chinese Journal of Diabetes
2025;33(8):610-616
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether CD137-CD137 ligand(CD137L)pathway affects foot ulcer wound healing in diabetic mice by regulating phenotypic transformation of macrophages.Methods A total of 24 db/db mice were randomly divided into model(Mod),CD137 and anti-CD137 groups with 8 mice in each group,and 8 db/m mice were selected as control(Con)group.Ulcer wounds were prepared in each group.The wound healing rate was calculated at the 7,14 and 21 day in each group.The pathological changes of the wound were evaluated by HE staining.The levels of serum IL-1β,TNF-α,VEGF and basic fibroblast growth factor(bFGF)were detected by ELISA,and the expression of wound angiogenesis marker CD31 was detected by immunofluorescence staining.The expression of the gene-induced nitric oxide synthase(iNOS),IL-6 in M1-type macrophages and arginase 1(Arg1),mannose receptor(CD206)in M2-type macrophages were detected by qRT-PCR.Flow cytometry was used to detect the proportion of M1 macrophages labeled F4/80 and CD86,and the proportion of M2 macrophages labeled F4/80 and CD206 in peripheral blood of mice in each group.Results Compared with Mod group,the skin tissue structure was more complete,inflammatory cell infiltration was reduced,new hair follicle tissues were increased,the wound healing rate of CD137 group at 7,14 and 21 d,VEGF,bFGF,the relative fluorescence intensity of CD31 in wound tissue,the mRNA expression of Arg1 and CD206,and the proportion of M2-type macrophages were increased(P<0.05),IL-1β,TNF-α,the mRNA expression of iNOS and IL-6 expression,and the proportion of M1-type macrophages in peripheral blood were decreased in CD137 group(P<0.05).Conclusions CD137-CD137L pathway may play a role in promoting wound healing in DFU mice by promoting the transformation of wound macrophage phenotype M1 to M2.
