title: Preventive effects and mechanisms of rhein on renal interstitial fibrosis in obstructive nephropathy.
abstract: Renal interstitial fibrosis is a common outcome of a variety of chronic renal diseases. Here we evaluated the therapeutic efficacy of rhein on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) and investigated the potential mechanisms. Mice underwent UUO, followed by orally administrated rhein (150 mg/kg/d) or control vehicle. Renal interstitial injury and the degree of fibrosis were evaluated by pathological staining and Western blot. The possible mechanisms were studied by Western blot, indirect immune-fluorescence and enzyme-linked immunosorbent assay. Our results showed that rhein therapy markedly ameliorated renal interstitial fibrotic lesions, reduced α-smooth muscle actin (α-SMA) expression, attenuated deposition of fibronectin (FN). Rhein also suppressed transforming growth factor-β1 (TGF-β1) and its type I receptor expression in obstructed kidneys. In vitro, rhein abolished the α-SMA and fibronectin expression of rat kidney interstitial fibroblasts cells (NRK-49F) induced by TGF-β1. These observations strongly suggest that rhein is a potent inhibitor of renal interstitial fibrosis, and its therapeutic mechanism is, at least in part, blocking interstitial fibroblasts cells activation.
authors.affiliation: First Clinical Medical College of Nanjing Medical University, Nanjing 210029, P. R. China.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Lee
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012250:Rheum / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D000880:Anthraquinones; D005353:Fibronectins; D010936:Plant Extracts; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; C020491:rhein