Podocyte apoptosis is suppressed by 1,25(OH)2D3 in puromycin aminonudeoside nephropathy rats
- VernacularTitle:1,25(OH)2D3抑制嘌呤霉素氨基核苷酸肾病大鼠足细胞凋亡
- Author:
Houqin XIAO
;
Wei SHI
;
Shuangxin LIU
;
Wenjian WANG
;
Xinling LIANG
;
Yongzheng LIANG
;
Qiuxiong LIN
- Publication Type:Journal Article
- Keywords:
Pedocytes;
Transforming growth factor beta1;
Puromycin aminonucleoside;
Calcitriol
- From:
Chinese Journal of Nephrology
2008;24(12):890-896
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the effects of 1,25(OH)zD3 on podocyte apoptosis in kidney of puremyein aminonueleoside nephropathy (PAN) rats. Methods Seventy-two male Sprague-Dawley rats were randomly divided into three groups: PAN model group(PAN), 1,25 (OH)2D3 treated group (T, 0.2 μg·kg-1d-1 by garages) and normal control group (NC). PAN rat model was constructed by a single intravenous injection of 100 mg/kg body weight. Renal function and 24hour urinary protein were measured at day 3, 7, 14, 21 after PAN injection. The renal tissue morphology was observed by light and electron microscope. Podocyte apeptosis was evaluated by TUNEL. Protein expressions of nephrin, TGF-β1 and p-Smad2/3 were examined by immunofluoreacence, immunohistochemistry and Western blot, respectively. Results(1)The levels of serum creafinine, BUN and 24-h urinary protein [(20.26±4.87) mg vs (1.01±0.41) mg at day 7, P ＜0.01] were significantly higher and the number of glomerular pedocyte was significantly lower [(10.9±4.2)/glomerular volume vs (31.9±6.2)/glomerular volume at day 14, P＜0.01] in PAN group compared with NC group. T group rats had less urinary protein excretion [(9.95±3.82) mg/24 h, P＜0.01] and more glomerular podocytes compared with PAN group. (2) Distribution of nephrin expression was changed from linear to granular pattern in PAN rats on day 7, nephrin mRNA and protein expressions were markedly decreased(P＜0.01), while the number of apoptotic podocyte was increased in PAN group(P＜0.01). However, higher nephrin expression and less apoptotic podocytes were found in T group (P＜0.01). (3) Compared with NC group, the mRNA and protein expression of TGF-β1 and p-Smad2/3 were higher in PAN group (P＜0.01), while 1,25 (OH)2D3 treatment abrogated PAN-induced changes in the expression of TGF-β1 and p-Smad2/3 (P＜0.01). Conclusions 1,25 (OH)2D3 can significantly suppress PAN-induced podocyte apoptosis and ameliorate proteinnuria. The beneficial effect of 1,25(OH)2D3 on podocyte may contribute to direct suppression of TGF-β signaling.
