title: Evodiamine might inhibit TGF-beta1-induced epithelial-mesenchymal transition in NRK52E cells via Smad and PPAR-gamma pathway.
abstract: Epithelial-mesenchymal transition (EMT) is involved in renal tubulointerstitial fibrosis. Transforming growth factor (TGF)-beta1 is the main inducer of EMT. Phosphorylation of Smad proteins and PPAR-gamma activation are required for the process of TGF-beta1-induced EMT. Evodiamine possesses anti-inflammatory, anti-obesity, anti-cancer, and anti-nociceptive effects. We have examined the effects of evodiamine in EMT induced by TGF-beta1 and the role of Smad and PPAR-gamma signal pathway in rat renal proximal tubular epithelial (NRK52E) cells in vitro. E-cadherin, alpha-smooth muscle actin (SMA), Smad 2 and PPAR-gamma mRNA and protein expressions were detected by real-time PCR and Western blot, respectively. NRK52E treated with TGF-beta1 for 48 h induced EMT, as evidenced by loss of E-cadherin and de novo expression of alpha-SMA. EMT was almost completely blocked by evodiamine and rosiglitazone. TGF-beta1 significantly increased Smad 2 expression and decreased PPAR-gamma expression in NRK52E cells compared with the control group, while evodiamine and rosiglitazone almost reversed these effects. These observations suggest that evodiamine and rosiglitazone inhibit TGF-beta1-induced EMT in NRK52E cells. Smad 2 and PPAR-gamma signal pathway might participate in the effects of evodiamine and rosiglitazone in EMT induced by TGF-beta1.
authors.affiliation: Department of Nephrology, Hainan General Hospital, Haikou, Hainan, 570311, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Wei
authors.forename: Zhuori
authors.initials: Z
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Yuan
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000199:Actins; D015820:Cadherins; D047495:PPAR gamma; D011799:Quinazolines; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat; C049639:evodiamine
keywords: PPAR-gamma; Smad; TGF-beta1; epithelial-mesenchymal transition; evodiamine