Tranilast modulates fibrosis, epithelial-mesenchymal transition and peritubular capillary injury in unilateral ureteral obstruction rats.
OBJECTIVE
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.
Kaneyama
Tomoki
T
Department of Histopathology, Shinshu University School of Medicine, Matsumoto, Japan.
Kobayashi
Satoshi
S
Aoyagi
Daiju
D
Ehara
Takashi
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D002196:Capillaries / Q000293:injuries; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000150:complications; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; C012293:tranilast