Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats

Subeq, Yi‐Maun; Ke, Chen-Yen; Lin, Ning; Lee, Chung‐Jen; Chiu, Yi-Han; Hsu, Bang‐Gee

doi:10.1016/j.cyto.2010.11.004

Cited by 30 publications

(24 citation statements)

References 23 publications

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“…Suramin Blocks Expression of Fibronectin and Collagen I in the Rat Model of Chlorhexidine GluconateInduced Peritoneal Fibrosis. Tissue fibrosis is characterized by accumulation of ECM components, such as fibronectin and collagen I, two major ECM proteins Subeq et al, 2011). As such, we examined the effect of suramin on their expression in rats with peritoneal fibrosis.…”

Section: Resultsmentioning

confidence: 99%

Suramin Inhibits the Development and Progression of Peritoneal Fibrosis

Xiong

Liu

Lü

et al. 2014

J Pharmacol Exp Ther

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Peritoneal fibrosis is one of the most serious complications in patients with peritoneal dialysis (PD) and is associated with the loss of peritoneal membrane ultrafiltration function. In this study, we investigated whether suramin, an inhibitor that blocks multiple growth factors by binding to their receptors, would prevent development of peritoneal fibrosis in a rat model. Rats were given a daily intraperitoneal injection of chlorhexidine gluconate (CG) for 3 weeks to induce peritoneal fibrosis. Administration of suramin at 5, 10, and 20 mg/kg dose-dependently attenuated peritoneal membrane thickening and expression of collagen I, fibronectin, and a-smooth muscle actin. Increased expression of transforming growth factor-b1 (TGF-b1) and phosphorylation of Smad3 was detected in fibrotic peritoneum and inhibited by suramin treatment. Suramin was also effective in blocking CG-induced phosphorylation of inhibitor of kB (IkB) and nuclear factor (NF)-kBp65, expression of several inflammatory cytokines, and infiltration of macrophages in the peritoneum. Moreover, suramin suppressed angiogenesis and expression of vascular endothelial growth factor, a molecule associated with angiogenesis in the injured peritoneum. Therefore, our results indicate that suramin treatment can effectively alleviate the development of peritoneal fibrosis by suppression of TGF-b1 signaling, inflammation, and angiogenesis, and suggest that suramin may have therapeutic potential for prevention of peritoneal fibrosis in PD patients.

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Section: Resultsmentioning

confidence: 99%

Suramin Inhibits the Development and Progression of Peritoneal Fibrosis

Xiong

Liu

Lü

et al. 2014

J Pharmacol Exp Ther

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“…147 In vitro studies revealed that production of TGF-β induced by high glucose concentrations in human peritoneal meso thelial cells is inhibited by angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers. 145,148 In addition, treatment with ACE inhibitors resulted in attenuation of fibrosis in animal models of EPS. 149 Furthermore, in patients on PD, ACE inhibitors seem to have a positive effect on peritoneal function; 150 however, a protective effect of ACE inhibitors has not been found on EPS.…”

Section: Biomarkersmentioning

confidence: 99%

Encapsulating peritoneal sclerosis: the state of affairs

et al. 2011

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Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD) with a 50% mortality rate. EPS is characterized by progressive and excessive fibrotic thickening of the peritoneum, leading to encapsulation of the bowels and intestinal obstruction. At present, EPS cannot be detected with certainty during its early stages; however, a progressive loss of ultrafiltration capacity often precedes its development. Studies that attempted to elucidate the pathogenesis of EPS have shown that the duration of exposure to PD fluids is the most important risk factor for EPS, and that young age and possibly the effects of peritonitis are additional contributory factors. The pathophysiology of EPS is probably best described as a multiple-hit process with a central role for transforming growth factor β. A form of EPS that develops shortly after kidney transplantation has also been recognized as a distinct clinical entity, and may be a common form of EPS in countries with a high transplantation rate. Criteria have been developed to identify EPS by abdominal CT scan at the symptomatic stage, but further clinical research is needed to identify early EPS in asymptomatic patients, to clarify additional risk factors for EPS and to define optimal treatment strategies.

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“…TGF-β1 plays a critical role in activation of myofibroblasts. Although inhibitors of TGF-β1 are effective in short-term animal models 58–62 , they are not suitable for long term therapy because of the significant role of TGF-β1 in homeostasis and repair. Hepatocyte growth factor (HGF) is a pleiotropic cytokine produced by hepatic stellate cells and implicated in liver regeneration and fibrosis.…”

Section: Progress In Developing Therapies For Liver Fibrosismentioning

confidence: 99%

Anti-fibrogenic strategies and the regression of fibrosis

Kisseleva

Brenner

2011

Best Practice & Research Clinical Gastroenterology

147

110

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Liver fibrosis is an outcome of many chronic diseases, and often results in cirrhosis, liver failure, and portal hypertension. Liver transplantation is the only treatment available for patients with advanced stage of fibrosis. Therefore, alternative methods are required to develop new strategies for anti-fibrotic therapy. Available treatments are designed to substitute for liver transplantation or bridge the patients, they include inhibitors of fibrogenic cytokines such as TGF-β1 and EGF, inhibitors of rennin angiotensin system, and blockers of TLR4 signaling. Development of liver fibrosis is orchestrated by many cell types. However, activated myofibroblasts remain the primary target for anti-fibrotic therapy. Hepatic stellate cells and portal fibroblasts are considered to play a major role in development of liver fibrosis. Here we discuss the origin of activated myofibroblasts and different aspects of their activation, differentiation and potential inactivation during regression of liver fibrosis.

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Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats

Cited by 30 publications

References 23 publications

Suramin Inhibits the Development and Progression of Peritoneal Fibrosis

Suramin Inhibits the Development and Progression of Peritoneal Fibrosis

Encapsulating peritoneal sclerosis: the state of affairs

Anti-fibrogenic strategies and the regression of fibrosis

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