TFEB
间充质干细胞
生物
自噬
癌症研究
炎症
细胞生物学
转录因子
糖尿病肾病
基因敲除
肾
免疫学
内分泌学
细胞凋亡
生物化学
基因
作者
Yujia Yuan,Lan Li,Lingling Zhu,Fei Liu,Xi Tang,Guangneng Liao,Jingping Liu,Jun Cheng,Younan Chen,Yanrong Liu
出处
期刊:Stem Cells
[Wiley]
日期:2020-01-10
卷期号:38 (5): 639-652
被引量:38
摘要
Abstract Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Chronic inflammation is recognized as a key causal factor in the development and progression of DN, and the imbalance of M1/M2 macrophages (Mφ) contributes to this process. Mesenchymal stem cells (MSCs) have been reported to prevent renal injuries via immune regulation in diabetic models, but whether these benefits are owing to the regulation of Mφ, and the underlying signaling pathways are unknown. Here, we showed that MSCs elicited Mφ into M2 phenotype and prevented renal injuries in DN mice, but these effects were abolished when the Mφ were depleted by clodronate liposomes (Lipo-Clod), suggesting that Mφ were necessary for renal protection of MSCs in DN mice. Moreover, the MSCs promoted M2 polarization was attributable to the activation of transcription factor EB (TFEB) and subsequent restore of lysosomal function and autophagy activity in Mφ. Furthermore, in vivo adoptive transfer of Mφin vivo (Mφ from DN + MSCs mice) or MφMSCs (Mφ cocultured with MSCs in vitro) to DN mice improved renal function. While, TFEB knockdown in Mφ significantly abolished the protective role of MφMSCs. Altogether, these findings revealed that MSCs suppress inflammatory response and alleviate renal injuries in DN mice via TFEB-dependent Mφ switch.
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