The role of survivin in podocyte injury induced by puromycin aminonucleoside.

The role of survivin in podocyte injury induced by puromycin aminonucleoside.
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生存素在嘌呤霉素氨基核苷诱导的足细胞损伤中的作用。

DOI:
10.3390/ijms15046657
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发表时间:
2014-04-17
影响因子:
5.6
通讯作者:
Ding J
Ding J
中科院分区:
生物学2区
文献类型:
--
作者:
Li X;Zhang X;Li X;Ding F;Ding J

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Survivin是凋亡抑制蛋白家族的一员,在肿瘤细胞中具有独特的促进有丝分裂和调节凋亡的作用。近年来的研究表明,Survivin在多种正常成体细胞中也有表达。本研究旨在探讨Survivin在终末分化上皮细胞-足细胞中的作用。采用Real-Time PCR、western blot和荧光共聚焦显微镜检测Survivin在正常和损伤小鼠足细胞中的表达和定位。在嘌呤霉素损伤的足细胞中,观察Survivin对足细胞的保护作用,以及转染Survivin siRNA下调Survivin表达和转染Survivin质粒瞬时过表达Survivin的作用。在足细胞中,PAN刺激Survivin和凋亡相关分子caspase 3的表达。siRNA敲低survivin基因表达可增加caspase 3的活化,诱导足细胞凋亡和肌动蛋白骨架的显著重排。此外,Survivin过表达抑制PAN诱导的足细胞凋亡和细胞骨架重排。我们的数据提供了证据,生存素在保护足细胞免受PAN诱导的凋亡中起着重要作用。Survivin相关的抗凋亡机制可能,至少部分地,通过激活caspase 3。
Survivin is a member of the inhibitor of apoptosis protein family, which uniquely promotes mitosis and regulates apoptosis in cancer cells. Recent studies have demonstrated that survivin also expresses in several normal adult cells. In the present study, we aimed to investigate the function of survivin in the terminally differentiated epithelial cells, podocytes. Survivin expression and location were detected by Quantitative Real-Time PCR, western blot and fluorescence confocal microscopy methods in normal and injured mouse podocytes. Cyto-protection function of survivin was also studied in cultured podocyte injured by puromycin aminonucleoside (PAN), transfected with survivin siRNA to down-regulate survivin expression, or with survivin plasmid to transiently over-express survivin. In podocytes, PAN stimulated expressions of survivin and the apoptosis related molecule caspase 3. Knockdown of survivin expression by siRNA increased the activation of caspase 3, induced podocyte apoptosis and remarkable rearrangement of actin cytoskeleton. Moreover, over-expression of survivin inhibited PAN-induced podocyte apoptosis and cytoskeleton rearrangement. Our data provides the evidence that survivin plays an important role in protecting podocytes from apoptosis induced by PAN. The mechanism of survivin related anti-apoptosis may, at least partially, be through the activation of caspase 3.
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