Human umbilical cord mesenchymal stem cell attenuates renal fibrosis via TGF-β/Smad signaling pathways in vivo and in vitro

Eur J Pharmacol. 2020 Sep 15;883:173343. doi: 10.1016/j.ejphar.2020.173343. Epub 2020 Jul 3.

Abstract

Renal fibrosis is a progressive pathological process that eventually leads to end-stage renal failure with limited therapeutic options. The aim of this study was to investigate the nephron-protective effect of human umbilical cord mesenchymal stem cells (ucMSCs) on renal fibrosis. UcMSCs were intravenously injected into renal fibrosis mice induced by aristolochic acid (AA) and co-cultured with HK-2 cells induced by TGF-β1, respectively. The kidney functions including serum creatinine (Scr) and blood urea nitrogen (BUN) levels, and histopathology were examined after treated with stem cells and normal saline as control. Immunohistochemical staining, immunofluorescent staining, and Western blot analysis were used to assessed the expression of proteins associated with epithelial to mesenchymal transition (EMT) and TGF-β/Smad signaling pathway. The results showed that ucMSCs effectively improved the kidney function and pathological structure, reduced AA-induced fibrosis and extracellular matrix deposition. Besides, UcMSCs significantly inhibited the EMT process and TGF-β1/Smad signaling pathway in AA-induced mice and TGF-β1-induced HK-2 cells compared to the control (p < 0.05). Our data suggested that ucMSCs play as a nephron-protective role in anti-fibrosis through inhibiting the activation of TGF-β1/Smad signaling pathway.

Keywords: Aristolochic acid; Epithelial to mesenchymal transition; Mesenchymal stem cell; Renal fibrosis; TGF-β/Smad signaling pathway.

MeSH terms

  • Animals
  • Aristolochic Acids
  • Cell Line
  • Coculture Techniques
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Fibrosis
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / surgery*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mice, Inbred C57BL
  • Phosphorylation
  • Recovery of Function
  • Signal Transduction
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • Umbilical Cord / cytology

Substances

  • Aristolochic Acids
  • Smad Proteins
  • TGFB1 protein, human
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • aristolochic acid I