title: Effects of Bone Marrow Mesenchymal Stem Cells on Plasminogen Activator Inhibitor-1 and Renal Fibrosis in Rats with Diabetic Nephropathy.
abstract: We undertook this study to observe the effects of bone marrow mesenchymal stem cells (BMSCs) on plasminogen activator inhibitor-1 (PAI-1) and renal fibrosis in rats with diabetic nephropathy and to explore its main mechanism.
  
  
  
  Thirty male Sprague Dawley rats were randomly divided into three groups: normal control group (NC group, n = 10), diabetic nephropathy group (DN group, n = 10), stem cell transplantation group (MSC group, n = 10). BMSCs were transplanted to rats in the MSC group via caudal vein infusion (2 × 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 β1 (TGF-β1) and Smad3 in rat kidney were detected by immunohistochemistry and Western blot.
  
  
  
  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-β1 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 PAI-1 and TGF-β1 (r = 0.987, p <0.05) and Smad3 (r = 0.974, p <0.05) showed a significant positive correlation. TGF-β1 and Smad3 (r = 0.962, p <0.05) were positively correlated.
  
  
  
  BMSCs significantly inhibited renal fibrosis in rats with DN. The mechanism may be related to inhibition of TGF-β1/Smad3 pathway, decreasing the expression of PAI-1 protein and reducing the accumulation of extracellular matrix, thereby balancing the fibrinolytic system.
authors.affiliation: Department of Nephrology, Affiliated Hospital of Xuzhou Medical College, Hospital of Xuzhou Medical College, xuzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lang
authors.affiliation: Department of Nephrology, Affiliated Hospital of Xuzhou Medical College, Hospital of Xuzhou Medical College, xuzhou, China. Electronic address: 444085089@qq.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Dai
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D003094:Collagen; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis; D007668:Kidney / Q000473:pathology*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D003094:Collagen
keywords: Bone marrow mesenchymal stem cells; Diabetic nephropathy; Plasminogen activator inhibitor-1; Renal fibrosis; Transforming growth factor-β1/Smad3 signaling pathway