title: Protective effect of epigallocatechin-3-gallate (EGCG) via Nrf2 pathway against oxalate-induced epithelial mesenchymal transition (EMT) of renal tubular cells.
abstract: This study evaluated effect of oxalate on epithelial mesenchymal transition (EMT) and potential anti-fibrotic property of epigallocatechin-3-gallate (EGCG). MDCK renal tubular cells were incubated with 0.5 mM sodium oxalate for 24-h with/without 1-h pretreatment with 25 μM EGCG. Microscopic examination, immunoblotting and immunofluorescence staining revealed that oxalate-treated cells gained mesenchymal phenotypes by fibroblast-like morphological change and increasing expression of vimentin and fibronectin, while levels of epithelial markers (E-cadherin, occludin, cytokeratin and ZO-1) were decreased. EGCG pretreatment could prevent all these changes and molecular mechanisms underlying the prevention by EGCG were most likely due to reduced production of intracellular ROS through activation of Nrf2 signaling and increased catalase anti-oxidant enzyme. Knockdown of Nrf2 by small interfering RNA (siRNA) abrogated all the effects of EGCG, confirming that the EGCG protection against oxalate-induced EMT was mediated via Nrf2. Taken together, our data indicate that oxalate turned on EMT of renal tubular cells that could be prevented by EGCG via Nrf2 pathway. These findings also shed light onto development of novel therapeutics or preventive strategies of renal fibrosis in the future.
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Rattiyaporn
authors.initials: R
authors.lastname: Kanlaya
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Supaporn
authors.initials: S
authors.lastname: Khamchun
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Chompunoot
authors.initials: C
authors.lastname: Kapincharanon
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Visith
authors.initials: V
authors.lastname: Thongboonkerd
mesh_terms: D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005355:Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D010070:Oxalates / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051267:NF-E2-Related Factor 2; D010070:Oxalates; D034741:RNA, Small Interfering; D002392:Catechin; C045651:epigallocatechin gallate