医学
福克斯M1
伤口愈合
糖尿病足溃疡
基因敲除
基因沉默
刺猬信号通路
内科学
细胞生物学
巨噬细胞极化
癌症研究
信号转导
免疫学
糖尿病
内分泌学
细胞凋亡
生物
体外
糖尿病足
细胞周期
巨噬细胞
生物化学
癌症
基因
作者
Yang Yang,Bo Zhang,Yufan Yang,Bibo Peng,Rui Ye
标识
DOI:10.1016/j.diabres.2021.109121
摘要
The diabetic wound environment is accompanied with prolonged inflammation leading to impaired wound healing in diabetic foot ulcer (DFU). Our study illustrated the molecular mechanisms by which Forkhead box M1 (FOXM1) enhanced M2 polarization and wound healing of DFU.Diabetes was modeled in vivo by streptozotocin injection in rats and in vitro by exposure to high glucose in human dermal fibroblasts (HDF). Macrophages were exposed to IL-4 to induce M2 phenotype polarization. Ectopic expression or knockdown of FOXM1 was performed to observe collagen deposition, angiogenesis, the proliferation and migration of HDF, as well as macrophage polarization.FOXM1 was lowly expressed in the wound tissue of DFU rats. In vitro experiments showed that silencing FOXM1 reversed the M2 polarization-induced promotion of HDF proliferation and migration. We further found that FOXM1 bound to the promoter region of SEMA3C to elevate its expression, and SEMA3C upregulated NRP2 and activated the Hedgehog signaling pathway. Silencing of SMO, a signal transducer in the Hedgehog pathway, negated the promoting effect of FOXM1 overexpression in M2 polarization and HDF proliferation.Thus, our results suggest that targeting transcription factor FOXM1 may provide a therapeutic target for promoting wound healing in DFU.
科研通智能强力驱动
Strongly Powered by AbleSci AI