Signaling and regulatory mechanisms of integrinα3β1 on the apoptosis of cultured rat podocytes

被引:17
作者
Chen, Chien-An
Tsai, Jer-Chia
Su, Pin-Wen
Lai, Yung-Hsiung
Chen, Hung-Chun
机构
[1] Kaohsiung Med Univ, Dept Internal Med, Div Nephrol, Grad Inst Med, Kaohsiung 807, Taiwan
[2] Kaohsiung Med Univ, Dept Nephrol, Kaohsiung 807, Taiwan
[3] Enfield Med Co, Kaohsiung, Taiwan
来源
JOURNAL OF LABORATORY AND CLINICAL MEDICINE | 2006年 / 147卷 / 06期
关键词
D O I
10.1016/j.lab.2005.12.010
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Integrin is the major adhesion molecule for the attachment of podocytes to the glomerular basement membrane, and integrins have been shown to play a major role in the regulation of cell survival. In this study, the authors investigated the apoptosis and its related signal pathways to integrin in cultured rat podocytes. Apoptosis was detected with the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. Cytochrome c was examined by immunohistochemical stain, and Fas, Fas ligand, Bax, Bcl-2, and ERK activation (p-ERK/ERK) were analyzed by Western blotting analysis. The results demonstrated that the integrin antagonist, Gly-Arg-Gly-Asp (GRGD), increased the percentage of cells with apoptosis (from 0.9 +/- 0.5% to 27.2 +/- 9.9%, P < 0.01). Inhibition of protein tyrosine kinase With genistein also caused apoptosis of podocytes (from 0.9 +/- 0.5% to 26.0 +/- 8.7%, P < 0.01). In GRGD-treated cells, cytochrome c was found released into cytoplasm by immunohistochemical study and the Bax expression was upregulated, whereas Bcl-2 expression was not changed. Fas was not expressed in both control and GRGD-treated podocytes, although Fas ligand was upregulated in GRGD-treated cells. ERK activation was also found to be increased in GRGD-treated cells. The results indicated that alpha 3 beta 1integrin is necessary for the prevention of the apoptosis of cultured rat podocytes, and that the signaling involves the Bax, Bcl-2, and cytochrome c pathways.
引用
收藏
页码:274 / 280
页数:7
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