Effects of Bone Marrow Mesenchymal Stem Cells on Plasminogen Activator Inhibitor-1 and Renal Fibrosis in Rats with Diabetic Nephropathy

Background and Aims. We undertook this study to observe the effects of bone marrow mesenchymal stem cells (BMSCs) on plasminogen activator inhibitor-1 (PM-1) and renal fibrosis in rats with diabetic nephropathy and to explore its main mechanism. Methods. Thirty male Sprague Dawley rats were randomly divided into three groups: normal control group (NC group, n = 10), diabetic nephropathy group (DN group, 77 = 10), stem cell transplantation group (MSC group, n = 10). BMSCs were transplanted to rats in the MSC group via caudal vein infusion (2 x 10(6)/mL). At the end of 12 weeks, blood glucose, 24-h urinary protein, serum creatinine and renal mass index were measured. Morphology and collagen deposition in rat kidney were observed by HE and Masson staining, respectively. Expressions of PAI-1, transforming growth factor beta 1 (TGF-beta 1) and Smad3 in rat kidney were detected by immunohistochemistry and Western blot. Results. Compared with DN group, 24-h protein, serum creatinine and renal mass index decreased significantly in MSC group. No significant changes in blood glucose (p > 0.05) were shown Immunohistochemistry and Western blot showed that expressions of PAI-1, TGF-beta 1 and Smad3 in NC group were lower than DN group. Expression of each protein in MSC group was between two groups (p < 0.05). Correlation analysis revealed that PM-1 and TGF-beta 1 (r = 0.987, p < 0.05) and Smad3 (r = 0.974, p < 0.05) showed a significant positive correlation. TGF-131 and Smad3 (r = 0.962, p < 0.05) were positively correlated. Conclusions. BMSCs significantly inhibited renal fibrosis in rats with DN. The mechanism may be related to inhibition of TGF-beta 1/Smad3 pathway, decreasing the expression of PAI-1 protein and reducing the accumulation of extracellular matrix, thereby balancing the fibrinolytic system. (C) 2016 IMSS. Published by Elsevier Inc.