title: Suramin inhibits the development and progression of peritoneal fibrosis.
abstract: 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 α-smooth muscle actin. Increased expression of transforming growth factor-β1 (TGF-β1) 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 κB (IκB) and nuclear factor (NF)-κBp65, 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-β1 signaling, inflammation, and angiogenesis, and suggest that suramin may have therapeutic potential for prevention of peritoneal fibrosis in PD patients.
authors.affiliation: Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (C.X., N.L., L.F., S.Z., H.Y.); and Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island (S.Z.).
authors.forename: Chongxiang
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (C.X., N.L., L.F., S.Z., H.Y.); and Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island (S.Z.) yhdcmu@sina.com szhuang@lifespan.org.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (C.X., N.L., L.F., S.Z., H.Y.); and Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island (S.Z.).
authors.forename: Lu
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (C.X., N.L., L.F., S.Z., H.Y.); and Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island (S.Z.) yhdcmu@sina.com szhuang@lifespan.org.
authors.forename: Shougang
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (C.X., N.L., L.F., S.Z., H.Y.); and Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island (S.Z.) yhdcmu@sina.com szhuang@lifespan.org.
authors.forename: Haidong
authors.initials: H
authors.lastname: Yan
mesh_terms: D000199:Actins / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005353:Fibronectins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D043925:Angiogenesis Inducing Agents; D024042:Collagen Type I; D016207:Cytokines; D005353:Fibronectins; D051900:Smad3 Protein; D013498:Suramin; D053773:Transforming Growth Factor beta1; C497787:Smad3 protein, rat; C498862:Acta2 protein, rat