Age-related progressive renal fibrosis in rats and its prevention with ACE inhibitors and taurine

Am J Physiol Renal Physiol. 2000 Jan;278(1):F122-9. doi: 10.1152/ajprenal.2000.278.1.F122.

Abstract

Our previous studies demonstrated an increased reactive oxygen species (ROS) production, as well as transforming growth factor-beta1 (TGF-beta1) expression in the rat kidney with aging. In the present study, we examined the effect of aging on extracellular matrix (ECM) accumulation and the effects of treatment with angiotensin-converting enzyme inhibitors (captopril and lisinopril) and taurine, an antioxidant amino acid. Age-related increases in types I and IV collagen and fibronectin mRNA expression were found at 24 and 30 mo of age. In contrast, type III collagen only increased in 30-mo-old rats. Captopril-, lisinopril-, and taurine-treated animals showed a statistically significant decrease in ECM protein expression at both ages. Moreover, treatment with taurine reduced the TGF-beta1 mRNA levels in 24- and 30-mo-old rats by 40%. Taurine also completely blocked increases in type I and type IV collagen expression in mesangial cells in response to TGF-beta1. Our results demonstrate a protective role from both converting enzyme inhibitors and taurine in the age-related progressive renal sclerosis. In addition, taking into account that taurine is considered as an antioxidant amino acid, present data suggest a role for ROS in age-related progressive renal fibrosis, perhaps through interactions with the TGF-beta1 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Antioxidants / therapeutic use*
  • Captopril / therapeutic use
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Fibrosis
  • Kidney Cortex / metabolism*
  • Kidney Cortex / pathology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / prevention & control
  • Lisinopril / therapeutic use
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Taurine / therapeutic use
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antioxidants
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Taurine
  • Captopril
  • Lisinopril