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

Arch Med Res. 2016 Feb;47(2):71-7. doi: 10.1016/j.arcmed.2016.03.002. Epub 2016 Mar 24.

Abstract

Background and aims: 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.

Methods: 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.

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-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.

Conclusions: 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.

Keywords: Bone marrow mesenchymal stem cells; Diabetic nephropathy; Plasminogen activator inhibitor-1; Renal fibrosis; Transforming growth factor-β1/Smad3 signaling pathway.

MeSH terms

  • Animals
  • Bone Marrow Cells / pathology*
  • Collagen
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology*
  • Fibrosis
  • Kidney / pathology*
  • Male
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Smad3 Protein / metabolism
  • Streptozocin
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Plasminogen Activator Inhibitor 1
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta1
  • Streptozocin
  • Collagen