Macrophages Regulate Renal Fibrosis Through Modulating TGFβ Superfamily Signaling

被引:112
作者
Shen, Bing [1 ,2 ]
Liu, Xiuheng [1 ]
Fan, Yu [2 ]
Qiu, Jianxin [2 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Urol, Wuhan 430060, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Urol, Shanghai Peoples Hosp 1, Shanghai 200030, Peoples R China
关键词
macrophages; unilateral ureteral obstruction; renal fibrosis; epithelial-to-mesenchymal transition; transforming growth factor beta 1; bone morphogenic protein 7; E-cadherin; alpha-smooth muscle actin; UNILATERAL URETERAL OBSTRUCTION; TO-MESENCHYMAL TRANSITION; TUBULOINTERSTITIAL FIBROSIS; ALTERNATIVE ACTIVATION; CLODRONATE; CELLS; BMP-7; RATS; MICE; INFILTRATION;
D O I
10.1007/s10753-014-9941-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Renal fibrosis is the fundamental pathway leading to end-stage renal disease, while its exact molecular basis remains incompletely elucidated. Previous studies have demonstrated that transforming growth factor beta 1 (TGF beta 1) is an inducer of the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells, while bone morphogenic protein 7 (BMP7) counteracts TGF beta 1-induced EMT and reverses chronic renal injury. Although macrophage recruitment is believed to play an important role during the whole pathogenesis, the mechanism underlying their activate involvement in the formation of renal fibrosis besides phagocytosizing extracellular matrix and apoptotic cells is largely unknown. Here, in a mouse unilateral ureteral obstruction (UUO) model, we show that the recruited macrophages are mainly M1 macrophages at early stage. However, these F4/80-positive and CD301-negative M1 macrophages were shortly polarized into F4/80-positive and CD301-positive M2 macrophages, respectively, which released high levels TGF beta 1, to contradict the local expression of BMP7 to facilitate EMT-induced renal fibrosis. M2 macrophages depletion specifically inhibited EMT, and subsequently the renal fibrosis. Adoptive transplantation of M2 macrophages increased the features of renal fibrosis. Our study thus identified double-edged effects of macrophages in the formation of renal fibrosis, which suggest that modulation of macrophage polarization may substantially improve the treatment of renal fibrosis.
引用
收藏
页码:2076 / 2084
页数:9
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