Pan Bixia, Liu Guohui, Jiang Zongpei, Zheng Dongwen
Department of Nephrology, Dongguan People's Hospital, Dongguan, China.
Cell Physiol Biochem. 2015;35(3):1062-9. doi: 10.1159/000373932. Epub 2015 Feb 2.
BACKGROUND/AIMS: Since renal fibrosis always predisposes end-stage renal disease, elucidation of the molecular mechanisms that underlie the progression of renal fibrosis may substantially improve the understanding and treatment for renal failure. Previous studies have highlighted an important counteraction between transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells during chronic renal injury. Macrophages are also believed to play a critical role in renal fibrosis. However, the relationship between macrophages and EMT is unknown.
Here, we used a mouse unilateral ureteral obstruction (UUO) model to address to these questions, and analyzed macrophage and its subpopulations purified by flow cytometry.
We found that the recruited macrophages are polarized to a M2 subtype after renal injury. M2 macrophages released high levels TGFβ1 to suppress BMP7 to enhance EMT-induced renal fibrosis. Depletion of M2 macrophages, but not of M1 macrophages, specifically inhibited EMT, and subsequently the renal fibrosis. Adoptive transplantation of M2 macrophages deteriorated renal fibrosis.
Thus, our study highlights M2 macrophages as a critical target for treating renal fibrosis.
背景/目的：由于肾纤维化往往是终末期肾病的诱因，阐明肾纤维化进展的分子机制可能会显著增进对肾衰竭的理解并改善其治疗方法。先前的研究强调了在慢性肾损伤期间，转化生长因子β1（TGFβ1）与骨形态发生蛋白7（BMP7）在肾小管上皮细胞上皮-间质转化（EMT）过程中的重要拮抗作用。巨噬细胞也被认为在肾纤维化中起关键作用。然而，巨噬细胞与EMT之间的关系尚不清楚。
在此，我们使用小鼠单侧输尿管梗阻（UUO）模型来解决这些问题，并通过流式细胞术分析纯化的巨噬细胞及其亚群。
我们发现，肾损伤后募集的巨噬细胞极化为M2亚型。M2巨噬细胞释放高水平的TGFβ1以抑制BMP7，从而增强EMT诱导的肾纤维化。耗竭M2巨噬细胞而非M1巨噬细胞可特异性抑制EMT，进而抑制肾纤维化。过继移植M2巨噬细胞会使肾纤维化恶化。
因此，我们的研究强调M2巨噬细胞是治疗肾纤维化的关键靶点。
