Department of General Surgery, Xingqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Biochem Biophys Res Commun. 2012 Aug 10;424(4):663-8. doi: 10.1016/j.bbrc.2012.07.003. Epub 2012 Jul 7.
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.
血管紧张素 II（Ang II）在细胞凋亡中起着重要作用。然而，Ang-II 诱导肠上皮细胞凋亡的机制尚不完全清楚。GATA-6 是一种在结直肠上皮细胞中表达的锌指转录因子，它指导细胞增殖、分化和凋亡。在本研究中，我们研究了 GATA-6 影响肠上皮细胞中 Ang-II 诱导凋亡的潜在机制。通过将 Caco-2 细胞与 Ang II 共培养建立体外肠上皮细胞凋亡模型。用血管紧张素 II 型受体拮抗剂 PD123319 预处理可显著降低 Bax 的表达，并防止 Ang II 诱导的 Caco-2 细胞凋亡。此外，Ang II 上调了 GATA-6 的表达。有趣的是，GATA-6 短发夹 RNA 可防止 Ang II 诱导的肠上皮细胞凋亡，并降低 Bax 的表达，但不降低 Bcl-2 的表达。综上所述，本研究表明，血管紧张素 II 通过 AT2 受体依赖性方式，通过 GATA-6 和 Bax 途径促进肠上皮细胞凋亡。
