title: Effect of mycophenolic acid on cyclosporin A-induced fibronectin expression in rat mesangial cells.
abstract: This study was undertaken to determine if mycophenolic acid (MPA) inhibits the profibrotic action of cyclosporin A (CsA) and, if so, to determine the molecular mechanisms involved. The effect of MPA treatment on CsA-induced signaling through the transforming growth factor-β (TGF-β)/Smad pathway was evaluated by immunoblot analysis in cultured primary rat mesangial cells. Treatment of cells with 1 µmol/l MPA did not significantly decrease the CsA-induced expression of TGF-β(1), but partially reversed the increases in Smad3 phosphorylation and fibronectin (FBN) production, and increased Smad7 expression. These results suggest that MPA may ameliorate CsA-induced FBN production by modulating the Smad signaling pathway. This study provides evidence that MPA can attenuate CsA-induced renal injury after kidney transplantation.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Joon-Sung
authors.initials: JS
authors.lastname: Park
authors.forename: Gheun-Ho
authors.initials: GH
authors.lastname: Kim
authors.forename: Chor Ho
authors.initials: CH
authors.lastname: Jo
authors.forename: Sua
authors.initials: S
authors.lastname: Kim
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Lee
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Chong Myung
authors.initials: CM
authors.lastname: Kang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016572:Cyclosporine / Q000008:administration & dosage*; D005353:Fibronectins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D005353:Fibronectins; D007166:Immunosuppressive Agents; D034741:RNA, Small Interfering; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D009173:Mycophenolic Acid