Amelioratory Effects of Testosterone Propionate on Age-related Renal Fibrosis via Suppression of TGF-β1/Smad Signaling and Activation of Nrf2-ARE Signaling

Sci Rep. 2018 Jul 16;8(1):10726. doi: 10.1038/s41598-018-29023-3.

Abstract

Androgen plays a pivotal role in the progression of renal fibrosis. However, whether exogenous androgen treatment to aged male rats can improve the age-related renal fibrosis was not explored. In our study, the changes of morphological structure, renal fibrosis, ultrastructure and renal function, the expressions of extracellular matrix (ECM), matrix metalloproteinases (MMPs) and its tissue inhibitors of metalloproteinases (TIMPs), the expressions of tumor growth factor β1 (TGF-β1)/Smad signaling and oxidative stress parameters as well as nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling were tested in kidney of aged male Wistar rats after subcutaneous testosterone propionate (TP, 2 mg/kg/d, 84-day) injection. Aged rats showed significantly renal histopathological changes, increased renal fibrosis, increased thickening of the glomerular basement membrane and the Bowman's capsule basement membrane, declined renal functional, increased ECM, lower expressions of MMP-2 and MMP-9 and higher expressions of TIMP-1 and TIMP-2 in renal tissues and higher expressions of TGF-β1/Smad signaling, as well as lower expressions of Nrf2-ARE signaling compared to young rats. TP treatment significantly improved age-related above indexes. These results suggested that TP supplement may alleviate age-related renal fibrosis via suppression of TGF-β1/Smad signaling and activation of Nrf2-ARE signaling in aged rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Antioxidant Response Elements / genetics
  • Fibrosis
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Kidney / drug effects
  • Kidney / pathology*
  • Kidney / ultrastructure
  • Male
  • Microscopy, Electron, Transmission
  • Models, Animal
  • NF-E2-Related Factor 2 / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Smad Proteins / metabolism
  • Testosterone Propionate / administration & dosage*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Smad Proteins
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Testosterone Propionate