| First Author | Ohgushi M | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 22 | Pages | 10017-28 |
| PubMed ID | 16260615 | Mgi Jnum | J:102384 |
| Mgi Id | MGI:3607434 | Doi | 10.1128/MCB.25.22.10017-10028.2005 |
| Citation | Ohgushi M, et al. (2005) Transforming growth factor beta-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. Mol Cell Biol 25(22):10017-28 |
| abstractText | Transforming growth factor beta (TGF-beta) has been implicated in the maintenance of homeostasis in various organs, including the gastric epithelium. In particular, TGF-beta-induced signaling was shown to be required for the differentiation-associated physiological apoptosis of gastric epithelial cells, but its mechanism has not been well understood. In this study, the molecular mechanism of TGF-beta-induced apoptosis was analyzed in a human gastric epithelial cell line, SNU16, as an in vitro model. Expression of Smad7 and Bcl-X(L), but not viral FLIP, was shown to prevent TGF-beta-induced apoptosis, indicating an exclusive requirement of the activation of Smad signaling pathway and mitochondrial dysfunction followed by activation of caspase-9. In addition, treatment with TGF-beta induced binding of Bim, a proapoptotic Bcl-2 homology domain 3 (BH3)-only protein, to Bcl-X(L), which is dependent on the activation of Smad, and reduction in the expression of Bim by RNA interference decreased the sensitivity to TGF-beta-induced apoptosis. Moreover, we found abnormalities in the gastric epithelium of both Bim and caspase-9 knockout mice; these abnormalities were associated with a defect of physiological apoptosis in gastric epithelial cells. These results indicate for the first time that TGF-beta is involved in the physiological loss of gastric epithelial cells by activating apoptosis mediated by Smad, Bim, and caspase-9. |
