Bone Marrow Mesenchymal Stem Cells Ameliorate Cisplatin-Induced Renal Fibrosis via miR-146a-5p/Tfdp2 Axis in Renal Tubular Epithelial Cells

Front Immunol. 2021 Feb 16:11:623693. doi: 10.3389/fimmu.2020.623693. eCollection 2020.

Abstract

Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury (AKI). However, the potential function of MSCs in chronic kidney disease remains elusive. Renal fibrosis is the common endpoint of chronic progressive kidney diseases and causes a considerable health burden worldwide. In this study, the protective effects of bone marrow mesenchymal stem cells (BM-MSCs) were assessed in repeated administration of low-dose cisplatin-induced renal fibrosis mouse model in vivo as well as a TGF-β1-induced fibrotic model in vitro. Differentially expressed miRNAs in mouse renal tubular epithelial cells (mRTECs) regulated by BM-MSCs were screened by high-throughput sequencing. We found microRNA (miR)-146a-5p was the most significant up-regulated miRNA in mRTECs. In addition, the gene Tfdp2 was identified as one target gene of miR-146a-5p by bioinformatics analysis. The expression of Tfdp2 in the treatment of BM-MSCs on cisplatin-induced renal injury was evaluated by immunohistochemistry analysis. Our results indicate that BM-MSC attenuates cisplatin-induced renal fibrosis by regulating the miR-146a-5p/Tfdp2 axis in mRTECs.

Keywords: TGF-β1; bone marrow mesenchymal stem cells; microRNA; renal fibrosis; renal tubular epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / pathology
  • Cisplatin / adverse effects*
  • Cisplatin / pharmacology
  • DNA-Binding Proteins / immunology*
  • Epithelial Cells / immunology*
  • Epithelial Cells / pathology
  • Fibrosis
  • Kidney Diseases* / chemically induced
  • Kidney Diseases* / immunology
  • Kidney Diseases* / pathology
  • Kidney Diseases* / therapy
  • Kidney Tubules / immunology*
  • Kidney Tubules / pathology
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / pathology
  • Mice
  • MicroRNAs / immunology*
  • Signal Transduction / immunology*
  • Transcription Factors / immunology*

Substances

  • DNA-Binding Proteins
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Tfdp2 protein, mouse
  • Transcription Factors
  • Cisplatin