Shasha Lv1, Gang Liu1, Aili Sun2, Jianping Wang3, Jing Cheng1, Weiwei Wang1, Xiangchun Liu1, Huibin Nie1, Guangju Guan4. 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.
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.
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 diabeticrats 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.
Authors: Futoshi Matsui; Stephen K Babitz; Audrey Rhee; Karen L Hile; Hongji Zhang; Kirstan K Meldrum Journal: Am J Physiol Renal Physiol Date: 2016-10-19
Authors: Fernando Ezquer; Maximiliano Giraud-Billoud; Daniel Carpio; Fabián Cabezas; Paulette Conget; Marcelo Ezquer Journal: Biomed Res Int Date: 2015-06-08 Impact factor: 3.411