| Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro. | |
| | |
MedLine Citation:
|
PMID: 20375980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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:
|
Zhao-Hong Chen; Wei-Song Qin; Cai-Hong Zeng; Chun-Xia Zheng; Yi-Mei Hong; Yi-Zhou Lu; Lei-Shi Li; Zhi-Hong Liu |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-10 |
Journal Detail:
|
Title: Kidney international Volume: 77 ISSN: 1523-1755 ISO Abbreviation: Kidney Int. Publication Date: 2010 Jun |
Date Detail:
|
Created Date: 2010-05-14 Completed Date: 2010-08-24 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
|
Languages: eng Pagination: 974-88 Citation Subset: IM |
Affiliation:
|
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Administration, Oral Animals Cell Line Complement Membrane Attack Complex / immunology* Cytoprotection Desmin / metabolism Disease Models, Animal Diterpenes / administration & dosage, adverse effects, pharmacology* Epoxy Compounds / administration & dosage, adverse effects, pharmacology Female Glomerulonephritis, Membranous / drug therapy*, immunology, pathology Heymann Nephritis Antigenic Complex / immunology Immunoglobulin G / blood Immunosuppressive Agents / administration & dosage, adverse effects, pharmacology* Mice NADPH Oxidase / metabolism Phenanthrenes / administration & dosage, adverse effects, pharmacology* Podocytes / drug effects*, immunology, pathology Proteinuria / immunology, pathology, prevention & control* Rabbits Rats Rats, Sprague-Dawley Rats, Wistar Reactive Oxygen Species / metabolism Signal Transduction / drug effects Tacrolimus / pharmacology Time Factors p38 Mitogen-Activated Protein Kinases / metabolism rho GTP-Binding Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Complement Membrane Attack Complex; 0/Desmin; 0/Diterpenes; 0/Epoxy Compounds; 0/Heymann Nephritis Antigenic Complex; 0/Immunoglobulin G; 0/Immunosuppressive Agents; 0/Phenanthrenes; 0/Reactive Oxygen Species; 109581-93-3/Tacrolimus; 38748-32-2/triptolide; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.6.5.2/RhoA protein, mouse; EC 3.6.5.2/rho GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Regulation of ion channels by secreted Klotho: mechanisms and implications.
Next Document: Encapsulating peritoneal sclerosis: incidence, predictors, and outcomes.