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Mesenchymal Stem Cells Elicit Macrophages into M2 Phenotype via Improving TFEB-mediated Autophagy to Alleviate Diabetic Nephropathy
STEM CELLS ( IF 5.2 ) Pub Date : 2020-01-10 , DOI: 10.1002/stem.3144
Yujia Yuan 1 , Lan Li 1 , Lingling Zhu 1 , Fei Liu 1 , Xi Tang 2 , Guangneng Liao 3 , Jingping Liu 1 , Jingqiu Cheng 1 , Younan Chen 1 , Yanrong Lu 1
Affiliation  

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.

中文翻译:

间充质干细胞通过改善 TFEB 介导的自噬诱导巨噬细胞进入 M2 表型以缓解糖尿病肾病

糖尿病肾病(DN)是终末期肾病的主要原因。慢性炎症被认为是 DN 发生和进展的关键因素,M1/M2 巨噬细胞 (Mφ) 的不平衡促成了这一过程。据报道,间充质干细胞 (MSCs) 可通过糖尿病模型中的免疫调节来预防肾损伤,但这些益处是否归因于 Mφ 的调节,以及潜在的信号通路尚不清楚。在这里,我们发现 MSCs 将 Mφ 诱导为 M2 表型并防止 DN 小鼠的肾损伤,但是当 Mφ 被氯膦酸脂质体 (Lipo-Clod) 耗尽时,这些作用被消除,表明 Mφ 对于 DN 中的 MSCs 的肾脏保护是必要的老鼠。而且,MSCs 促进 M2 极化归因于转录因子 EB (TFEB) 的激活和随后 Mφ 溶酶体功能和自噬活性的恢复。此外,将 Mφin vivo(来自 DN + MSCs 小鼠的 Mφ)或 MφMSC(Mφ 与体外 MSCs 共培养)过继转移至 DN 小鼠可改善肾功能。而 Mφ 中的 TFEB 敲低显着消除了 MφMSCs 的保护作用。总之,这些发现表明,MSCs 通过 TFEB 依赖性 Mφ 开关抑制炎症反应并减轻 DN 小鼠的肾损伤。Mφ 中的 TFEB 敲低显着消除了 MφMSCs 的保护作用。总之,这些发现表明,MSCs 通过 TFEB 依赖性 Mφ 开关抑制炎症反应并减轻 DN 小鼠的肾损伤。Mφ 中的 TFEB 敲低显着消除了 MφMSCs 的保护作用。总之,这些发现表明,MSCs 通过 TFEB 依赖性 Mφ 开关抑制炎症反应并减轻 DN 小鼠的肾损伤。
更新日期:2020-01-10
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