Age-related progressive renal fibrosis in rats and its prevention with ACE inhibitors and taurine.
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.
Cruz
C I
CI
Department of Physiology, Alcalá University, Madrid, Spain.
Ruiz-Torres
P
P
del Moral
R G
RG
Rodríguez-Puyol
M
M
Rodríguez-Puyol
D
D
D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D007672:Kidney Cortex / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000517:prevention & control; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013654:Taurine / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013654:Taurine; D002216:Captopril; D017706:Lisinopril