间充质干细胞通过分泌骨形态发生蛋白7抑制转化生长因子-β信号通路，在体内和体外改善糖尿病性肾小球纤维化。

Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7.

作者信息

Lv Shasha, Liu Gang, Sun Aili, Wang Jianping, Cheng Jing, Wang Weiwei, Liu Xiangchun, Nie Huibin, Guan Guangju

机构信息

Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.

Department of Endocrinology, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.

出版信息

Diab Vasc Dis Res. 2014 Jul;11(4):251-261. doi: 10.1177/1479164114531300. Epub 2014 May 19.

DOI:10.1177/1479164114531300

PMID:24845071

Abstract

PURPOSE

To investigate whether mesenchymal stem cells (MSCs) could inhibit transforming growth factor beta (TGF-β) signalling pathway by paracrine action.

METHODS

Bone marrow-derived MSCs were transplanted to streptozotocin-induced diabetic rats via tail vein. MSC-conditioned media were used with a model of mesangial cell fibrosis induced by high glucose in vitro.

RESULTS

At 8 weeks after MSC treatment, the renal function and the glomerulosclerosis as revealed by periodic acid Schiff stain was dramatically attenuated. The expression of collagen I, collagen IV and α-smooth muscle actin (SMA) in diabetic kidney was decreased, and E-cadherin increased after MSC treatment. The TGF-β signalling pathway was suppressed both in vivo and in vitro. MSCs secreted a significant amount of bone morphogenetic protein 7 (BMP7), in vitro, MSC-conditioned media inhibited TGF-β signalling stimulated by high glucose, and BMP7 neutralizing antibody blocked the inhibitory effect of MSC-conditioned media.

CONCLUSION

MSCs ameliorated glomerular fibrosis in vivo and in vitro by inhibiting TGF-β/Smad signalling pathway via secretion of BMP7.

摘要

目的

研究间充质干细胞（MSCs）是否可通过旁分泌作用抑制转化生长因子β（TGF-β）信号通路。

方法

将骨髓来源的MSCs经尾静脉移植到链脲佐菌素诱导的糖尿病大鼠体内。将MSCs条件培养基用于体外高糖诱导的系膜细胞纤维化模型。

结果

MSC治疗8周后，肾功能以及经高碘酸希夫染色显示的肾小球硬化显著减轻。糖尿病肾脏中I型胶原、IV型胶原和α-平滑肌肌动蛋白（SMA）的表达降低，而E-钙黏蛋白在MSC治疗后增加。TGF-β信号通路在体内和体外均受到抑制。MSCs分泌大量骨形态发生蛋白7（BMP7），体外，MSCs条件培养基抑制高糖刺激的TGF-β信号通路，且BMP7中和抗体阻断了MSCs条件培养基的抑制作用。