title: Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro.
abstract: Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiproteinuric properties, we established an experimental rat model of passive Heymann nephritis and a C5b-9 injury model of podocytes in vitro. Treatment or pretreatment with triptolide markedly reduced established proteinuria as well as the titer of circulating rat anti-rabbit IgG antibodies in these nephritic rats, accompanied by a reduction in glomerular C5b-9 deposits. Expression of desmin, a marker of podocyte injury, diminished after triptolide treatment, whereas quantitative analysis of mean foot process width showed that effacement of foot processes was substantially reversed. In in vitro studies we found that triptolide deactivated NADPH oxidase, suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase, and restored RhoA signaling activity. Triptolide did not interfere with the formation of C5b-9 on the membrane of podocytes. Thus, triptolide reduces established heavy proteinuria and podocyte injuries in rats with passive Heymann nephritis, and protects podocytes from C5b-9-mediated injury.
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Wei-Song
authors.initials: WS
authors.lastname: Qin
authors.forename: Cai-Hong
authors.initials: CH
authors.lastname: Zeng
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Zheng
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Hong
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Lu
authors.forename: Lei-Shi
authors.initials: LS
authors.lastname: Li
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D019610:Cytoprotection; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D026541:Heymann Nephritis Antigenic Complex / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D010616:Phenanthrenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D050199:Podocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011507:Proteinuria / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D015938:Complement Membrane Attack Complex; D003893:Desmin; D004224:Diterpenes; D004852:Epoxy Compounds; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; C001899:triptolide; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D016559:Tacrolimus