Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro.
Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.
Zheng
Chun-Xia
CX
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Chen
Zhao-Hong
ZH
Zeng
Cai-Hong
CH
Qin
Wei-Song
WS
Li
Lei-Shi
LS
Liu
Zhi-Hong
ZH
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D003599:Cytoskeleton / Q000187:drug effects; D003893:Desmin / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009401:Nephrosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010616:Phenanthrenes / Q000494:pharmacology*; D050199:Podocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011692:Puromycin Aminonucleoside / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D003893:Desmin; D004224:Diterpenes; D004852:Epoxy Compounds; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D014280:Triglycerides; C113267:nephrin; C001899:triptolide; D011692:Puromycin Aminonucleoside; D002784:Cholesterol