Li Meirong, Zhao Yali, Hao Haojie, Dong Liang, Liu Jiejie, Han Weidong, Fu Xiaobing
Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, China; Trauma Treatment Center, Central Laboratory, Hainan Branch, Chinese PLA General Hospital, Sanya, China.
Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, China.
Cytotherapy. 2017 Mar;19(3):371-383. doi: 10.1016/j.jcyt.2016.12.001. Epub 2017 Jan 9.
Chronic wounds are a common complication of diabetes. Fibroblast-myofibroblast differentiation is important for wound repair, which is commonly impaired in non-healing wounds, and the underlying mechanisms need to be further elucidated.
We used high glucose (HG) to simulated the diabetes microenvironment and explored its effects on the biological features of fibroblasts in vitro.
The results showed that prolonged HG induced senescence in fibroblasts through activation of p21 and p16 in a reactive oxygen species (ROS)-dependent manner, further delayed the viability and migration in fibroblasts and also depressed fibroblast differentiation through the TGF-β/Smad signaling pathway. However, mesenchymal stromal cell-conditioned medium (MSC-CM) counteracts the effects of HG. Treatment of fibroblasts with MSC-CM decreased HG-induced ROS overproduction, ameliorated HG-induced senescence in fibroblasts and reversed the defects in myofibroblast formation. Our results may provide clues for the pathogenesis of chronic wounds and a theoretical basis to develop MSC-CM as an alternative therapeutic method to treatment of chronic wounds.
慢性伤口是糖尿病的常见并发症。成纤维细胞向肌成纤维细胞的分化对伤口修复很重要，而在不愈合伤口中这种分化通常受损，其潜在机制有待进一步阐明。
我们使用高糖（HG）模拟糖尿病微环境，探讨其对体外成纤维细胞生物学特性的影响。
结果表明，长时间的HG通过以活性氧（ROS）依赖的方式激活p21和p16诱导成纤维细胞衰老，进一步延迟成纤维细胞的活力和迁移，并通过TGF-β/Smad信号通路抑制成纤维细胞分化。然而，间充质基质细胞条件培养基（MSC-CM）可抵消HG的作用。用MSC-CM处理成纤维细胞可减少HG诱导的ROS过度产生，改善HG诱导的成纤维细胞衰老，并逆转肌成纤维细胞形成的缺陷。我们的结果可能为慢性伤口的发病机制提供线索，并为开发MSC-CM作为治疗慢性伤口的替代治疗方法提供理论依据。
