Abstract
Aim: Tranilast is an anti-allergic compound suppressing transforming growth factor-beta 1 (TGF-β1) induced fibrosis. This study evaluated the efficacy of tranilast to attenuate renal fibrosis induced by unilateral ureteral obstruction (UUO) in rats in relation to epithelial-mesenchymal transition (EMT) and peritubular capillary injury.
Methods: Rats were divided into four groups: UUO with vehicle or tranilast and sham operation with vehicle or tranilast. Tranilast (400 mg/kg/day) was administrated to rats for 7 and 14 days after UUO.
Results: Fibrosis and tubular injuries were attenuated in UUO kidneys with tranilast (Tr-UUO kidneys) compared with UUO kidneys with vehicle (V-UUO kidneys). Decreased E-cadherin and increased vimentin expression in the tubular epithelium and Snail expression in V-UUO kidneys were also attenuated in Tr-UUO kidneys in which heparan sulfate proteoglycan in the tubular basement membrane was preserved and matrix metalloproteinase-2 expression was attenuated. Increased TGF-β1 and phospho-Smad2 expression and increased numbers of myofibroblasts and macrophages in V-UUO kidneys were attenuated by tranilast. Decreased VE-cadherin expression and cytoplasmic swelling of the endothelium of peritubular capillaries that occurred in V-UUO kidneys was prevented by tranilast.
Conclusions: Tranilast modulates fibrogenesis by reducing EMT, preventing disintegration of the tubular basement membrane, and reducing peritubular capillary injury in UUO kidneys.
Acknowledgements
The authors are grateful to the members of Department of Histopathology for their encouragement and helpful discussions, in particular to Ms T. Nishizawa and Ms M. Watanabe for their technical assistance.