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

• Published in: American journal of physiology. Renal physiology Vol. 278; no. 1; pp. F122 - F129
• Main Authors: Cruz, C I, Ruiz-Torres, P, del Moral, R G, Rodríguez-Puyol, M, Rodríguez-Puyol, D
• Format: Journal Article
• Language: English
• Published: United States 01.01.2000
• Subjects: 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; Rats; Rats, Inbred F344; RNA, Messenger - metabolism; Taurine - therapeutic use; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.2000.278.1.F122

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.