1, 25-dihydroxyvitamin D3 decreases adriamycin-induced podocyte apoptosis and loss.
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.


CONCLUSIONS
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.
Zou
Min-shu
MS
Department of Pediatrics, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
Yu
Jian
J
Nie
Guo-ming
GM
He
Wei-sun
WS
Luo
Li-man
LM
Xu
Hong-tao
HT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D004317:Doxorubicin; D053148:Caspase 3
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