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

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

doi:10.1177/1479164114531300

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

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

Authors

Shasha Lv¹, Gang Liu¹, Aili Sun², Jianping Wang³, Jing Cheng¹, Weiwei Wang¹, Xiangchun Liu¹, Huibin Nie¹, Guangju Guan⁴

Affiliations

¹ Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
² Department of Endocrinology, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
³ Department of Hemodialysis, Yuhuangding Hospital of Yantai City, Yantai, People's Republic of China.
⁴ Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China guangj@sdu.edu.cn.

PMID: 24845071
DOI: 10.1177/1479164114531300

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.

Keywords: Bone marrow mesenchymal stem cells; bone morphogenetic protein 7; diabetic nephropathy; fibrosis; transforming growth factor-β.