title: Age-related progressive renal fibrosis in rats and its prevention with ACE inhibitors and taurine.
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.
authors.affiliation: Department of Physiology, Alcalá University, Madrid, Spain.
authors.forename: C I
authors.initials: CI
authors.lastname: Cruz
authors.forename: P
authors.initials: P
authors.lastname: Ruiz-Torres
authors.forename: R G
authors.initials: RG
authors.lastname: del Moral
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Puyol
authors.forename: D
authors.initials: D
authors.lastname: Rodríguez-Puyol
mesh_terms: 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
chemical_list: 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