Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway
Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway
复制标题
血管紧张素II通过AT2受体、GATA-6和Bax途径诱导肠上皮细胞凋亡
DOI：
10.1016/j.bbrc.2012.07.003
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发表时间：
2012-08-10
影响因子：
3.1
通讯作者：
Yang, Hua
中科院分区：
文献类型：
--
作者：
Sun, Lihua;Wang, Wensheng;Yang, Hua
血管紧张素II（Angiotensin II，Ang II）在细胞凋亡中起重要作用。然而，Ang-II诱导肠上皮细胞凋亡的机制尚未完全清楚。加塔-6是一种在结肠直肠上皮中表达的锌指转录因子，其指导细胞增殖、分化和凋亡。本研究探讨了加塔-6对Ang-II诱导的肠上皮细胞凋亡的影响机制。采用血管紧张素Ⅱ（Ang Ⅱ）诱导Caco-2细胞凋亡，建立肠上皮细胞凋亡模型。AT 2受体拮抗剂PD 123319预处理可明显抑制Ang Ⅱ诱导的Caco-2细胞凋亡，降低Bax的表达。此外，Ang Ⅱ还上调了加塔-6的表达。有趣的是，加塔-6短发夹RNA阻止了血管紧张素II诱导的肠上皮细胞凋亡，并降低了Bax的表达，但没有Bcl-2。综上所述，本研究表明，血管紧张素II促进肠上皮细胞凋亡，通过加塔-6和Bax途径在AT 2受体依赖性的方式。(c)2012 Elsevier Inc. All rights reserved.
Angiotensin II (Ang II) has been shown to play an important role in cell apoptosis. However, the mechanisms of Ang-II-induced apoptosis in intestinal epithelial cells are not fully understood. GATA-6 is a zinc finger transcription factor expressed in the colorectal epithelium, which directs cell proliferation, differentiation and apoptosis. In the present study we investigated the underlying mechanism of which GATA-6 affects Ang-II induced apoptosis in intestinal epithelial cells. The in vitro intestinal epithelial cell apoptosis model was established by co-culturing Caco-2 cells with Ang II. Pretreatment with Angiotensin type 2 (AT2) receptor antagonist, PD123319, significantly reduced the expression of Bax and prevented the Caco-2 cells apoptosis induced by Ang II. In addition, Ang II up-regulated the expression of GATA-6. Interestingly, GATA-6 short hairpin RNA prevented Ang II-induced intestinal epithelial cells apoptosis and reduced the expression of Bax, but not Bcl-2. Taken together, the present study suggests that Angiotensin II promotes apoptosis in intestinal epithelial cells through GATA-6 and the Bax pathway in an AT2 receptor-dependent manner. (c) 2012 Elsevier Inc. All rights reserved.