Magnesium isoglycyrrhizinate ameliorates fructose-induced podocyte apoptosis through downregulation of miR-193a to increase WT1

Biochem Pharmacol. 2019 Aug:166:139-152. doi: 10.1016/j.bcp.2019.05.016. Epub 2019 May 11.

Abstract

High fructose intake is a risk of glomerular podocyte dysfunction. Podocyte apoptosis has emerged as a major cause of podocyte loss, exacerbating proteinuria. Magnesium isoglycyrrhizinate (MgIG) is usually used as a hepatoprotective agent in clinic. Liver and kidney injury often occurs in human diseases. Recent report shows that MgIG improves kidney function. In this study, we found that MgIG significantly alleviated kidney dysfunction, proteinuria and podocyte injury in fructose-fed rats. It also restored fructose-induced podocyte apoptosis in rat glomeruli and cultured differentiated podocytes. Of note, high-expression of miR-193a, downregulation of Wilms' tumor protein (WT1) and RelA, as well as upregulation of C-Maf inducing protein (C-mip) were observed in these animal and cell models. The data from the transfection of miR-193a mimic, miR-193a inhibitor, WT1 siRNA or LV5-WT1 in cultured differentiated podocytes showed that fructose increased miR-193a to down-regulate WT1, and subsequently activated C-mip to suppress RelA, causing podocyte apoptosis. These disturbances were significantly attenuated by MgIG. Taken together, these results provide the first evidence that MgIG restrains fructose-induced podocyte apoptosis at least partly through inhibiting miR-193a to upregulate WT1, supporting the application of MgIG with a novel mechanism-of-action against podocyte apoptosis associated with fructose-induced kidney dysfunction.

Keywords: High fructose intake; Magnesium isoglycyrrhizinate; MiR-193a; Podocyte apoptosis; WT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology
  • Fructose / toxicity*
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Podocytes / drug effects
  • Podocytes / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*
  • WT1 Proteins / metabolism*

Substances

  • 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate
  • Drugs, Chinese Herbal
  • MIRN193 microRNA, human
  • MicroRNAs
  • Saponins
  • Triterpenes
  • WT1 Proteins
  • Wt1 protein, rat
  • Fructose