title: Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway.
abstract: 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.
authors: Department of General Surgery, Xingqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Lihua
authors: L
authors: Sun
authors: Wensheng
authors: W
authors: Wang
authors: Weidong
authors: W
authors: Xiao
authors: Hongyin
authors: H
authors: Liang
authors: Yang
authors: Y
authors: Yang
authors: Hua
authors: H
authors: Yang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018938:Caco-2 Cells; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D050993:GATA6 Transcription Factor; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D051028:bcl-2-Associated X Protein; D000804:Angiotensin II; C073402:PD 123319