Amelioration of Diabetic Mouse Nephropathy by Catalpol Correlates with Down-Regulation of Grb10 Expression and Activation of Insulin-Like Growth Factor 1 / Insulin-Like Growth Factor 1 Receptor Signaling

PLoS One. 2016 Mar 17;11(3):e0151857. doi: 10.1371/journal.pone.0151857. eCollection 2016.

Abstract

Growth factor receptor-bound protein 10 (Grb10) is an adaptor protein that can negatively regulate the insulin-like growth factor 1 receptor (IGF-1R). The IGF1-1R pathway is critical for cell growth and apoptosis and has been implicated in kidney diseases; however, it is still unknown whether Grb10 expression is up-regulated and plays a role in diabetic nephropathy. Catalpol, a major active ingredient of a traditional Chinese medicine, Rehmannia, has been reported to possess anti-inflammatory and anti-aging activities and then used to treat diabetes. Herein, we aimed to assess the therapeutic effect of catalpol on a mouse model diabetic nephropathy and the potential role of Grb10 in the pathogenesis of this diabetes-associated complication. Our results showed that catalpol treatment improved diabetes-associated impaired renal functions and ameliorated pathological changes in kidneys of diabetic mice. We also found that Grb10 expression was significantly elevated in kidneys of diabetic mice as compared with that in non-diabetic mice, while treatment with catalpol significantly abrogated the elevated Grb10 expression in diabetic kidneys. On the contrary, IGF-1 mRNA levels and IGF-1R phosphorylation were significantly higher in kidneys of catalpol-treated diabetic mice than those in non-treated diabetic mice. Our results suggest that elevated Grb10 expression may play an important role in the pathogenesis of diabetic nephropathy through suppressing IGF-1/IGF-1R signaling pathway, which might be a potential molecular target of catalpol for the treatment of this diabetic complication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • GRB10 Adaptor Protein / biosynthesis
  • GRB10 Adaptor Protein / physiology*
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / physiology*
  • Iridoid Glucosides / pharmacology
  • Iridoid Glucosides / therapeutic use*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction
  • Receptor, IGF Type 1 / metabolism
  • Receptor, IGF Type 1 / physiology*

Substances

  • Drugs, Chinese Herbal
  • Grb10 protein, mouse
  • Hypoglycemic Agents
  • Iridoid Glucosides
  • GRB10 Adaptor Protein
  • catalpol
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1

Grant support

This work was supported by National Key Clinical Specialties Construction Program of China (No. [2013]544), The Chongqing Postgraduate Research Innovation Project (CYS14120). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.