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.

Glomerulosclerosis and Tubulointerstitial Fibrosis are Attenuated with 17β-Estradiol in the Aging Dahl Salt Sensitive Rat

“…Glomerulosclerosis and tubulointerstitial fibrosis in 4M and 12M DSS rats aging (17,23,37). Recent studies have shown that in addition to excessive synthesis of the ECM, the presence of amorphous ECM deposits in progressive renal disease are due to decreased activity of the ECM degradative pathway (38,39).…”

“…The aging kidney is characterized by a decrease in GFR and renal blood flow (11)(12)(13), decreased urine-concentrating ability (14), increased responsiveness to angiotensin II and endothelin (15)(16)(17), decreased production of vasodilatory prostaglandins and nitric oxide (18,19), increased oxidative stress (20,21), and increased glomerulosclerosis and tubulointerstitial fibrosis (22,23). Glomerulosclerosis and tubulointerstitial fibrosis are hallmarks of progressive renal disease from diverse etiologies, and these renal pathologies are frequently observed in kidneys from aging animals and humans (17,22,23). Most studies have concentrated on the mechanisms underlying age-related glomerular changes, whereas the agerelated changes in the tubulointerstitium have received far less attention.…”

Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria

“…Therefore, renal transsulfuration is important for Hcy clearance; it is responsible for the removal of ϳ20% of Hcy from the blood circulation in rats (10), and 78% of L-Hcy (added to the culture) was metabolized through the transsulfuration in isolated rat kidney cortical tubules (29). Meanwhile, there is accumulating evidence that several antioxidant Cys metabolites, such as glutathione (GSH, a reduced form), taurine, and hydrogen sulfide (H 2 S), exert protective effects against renal ischemia-reperfusion injury (9,24,48,74) and the progression of renal fibrosis (14,36,47).…”

Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure

“…One of the early events of the ECM remodeling process is the activation of matrix metalloproteinases (MMPs) (8,39). Among MMPs, elastinases and collagenases are particularly important of matrix degradation in fibrotic occlusive diseases including renal fibrosis (5,21).…”