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


CONCLUSIONS
MSCs ameliorated glomerular fibrosis in vivo and in vitro by inhibiting TGF-β/Smad signalling pathway via secretion of BMP7.
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Shasha
S
Lv
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Gang
G
Liu
Department of Endocrinology, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Aili
A
Sun
Department of Hemodialysis, Yuhuangding Hospital of Yantai City, Yantai, People's Republic of China.
Jianping
J
Wang
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Jing
J
Cheng
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Weiwei
W
Wang
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Xiangchun
X
Liu
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
Huibin
H
Nie
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China guangj@sdu.edu.cn.
Guangju
G
Guan
Bone marrow mesenchymal stem cells; bone morphogenetic protein 7; diabetic nephropathy; fibrosis; transforming growth factor-β