Document Detail


1, 25-dihydroxyvitamin D3 decreases adriamycin-induced podocyte apoptosis and loss.
MedLine Citation:
PMID:  20827429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Selective proteinuria is frequently observed in glomerular diseases characterized by podocyte injury. Although, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)] has potential therapeutic effects on chronic kidney diseases through decreasing podocyte loss, the mechanism underlying the beneficial effects of 1,25(OH)(2)D(3) on podocytes remains still unknown. The present study tested the hypothesis that 1,25(OH)(2)D(3) directly reduced podocyte apoptosis and loss.
METHODS: Sprague-Dawley (SD) rats were randomly assigned into three groups: Adriamycin (ADR) group (n=15), ADR+1,25-(OH)(2)D(3) group (n=16), and control group (n=16). Rats in ADR+1,25-(OH)(2)D(3) group were treated with 1,25(OH)(2)D(3) for 8 weeks. The number of podocytes and foot process width (FPW) were detected by transmission electron microscopy. The number of apoptotic podocytes per glomerulus and that of apoptotic nuclei and caspase-3 activity in cultured podocytes were determined by TUNEL staining. The average number of podocytes per glomerulus was quantified by immunohistochemistry. Expressions of p-Smad2/3, p-Smad1/5/8, Fas, Fas-Associated protein with Death Domain (FADD), Bax, and Bcl-2 proteins were examined by Western blot assay.
RESULTS: Compared with control group, proteinuria, FPW, apoptotic podocytes, caspase-3 activity, the protein expressions of p-Smad2/3, Fas, FADD, and Bax were significantly increased, podocyte density, p-Smad1/5/8 and Bcl-2 expression were decreased in ADR group. 1,25(OH)(2)D(3) significantly reduced proteinuria, FPW, caspase-3 activity, expressions of p-Smad2/3, Fas, FADD, and Bax and apoptosis of podocytes, but increased serum albumin, number of viable podocytes , p-Smad1/5/8 and Bcl-2 expression in ADR treated rats.
CONCLUSION: ADR-induced podocyte apoptosis was associated with the imbalance of p-Smad2/3, p-Smad1/5/8 the activity of caspase-3 and aberrant expressions of, Fas, FADD, Bax and Bcl-2. The beneficial effects of 1,25(OH)(2)D(3 )on podocytes may be attributable to inhibit podocyte apoptosis and the amelioration of podocytopenia.
Authors:
Min-shu Zou; Jian Yu; Guo-ming Nie; Wei-sun He; Li-man Luo; Hong-tao Xu
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Publication Detail:
Type:  Journal Article     Date:  2010-08-24
Journal Detail:
Title:  International journal of medical sciences     Volume:  7     ISSN:  1449-1907     ISO Abbreviation:  Int J Med Sci     Publication Date:  2010  
Date Detail:
Created Date:  2010-09-09     Completed Date:  2010-12-10     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101213954     Medline TA:  Int J Med Sci     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  290-9     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Blotting, Western
Caspase 3 / metabolism
Cells, Cultured
Doxorubicin / pharmacology*
Immunohistochemistry
Male
Microscopy, Electron, Transmission
Podocytes / cytology*,  drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Vitamin D / analogs & derivatives*,  pharmacology
Chemical
Reg. No./Substance:
0/dihydroxy-vitamin D3; 1406-16-2/Vitamin D; 23214-92-8/Doxorubicin; EC 3.4.22.-/Caspase 3
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