| First Author | Dünker N | Year | 2002 |
| Journal | Gastroenterology | Volume | 122 |
| Issue | 5 | Pages | 1364-75 |
| PubMed ID | 11984523 | Mgi Jnum | J:76342 |
| Mgi Id | MGI:2179162 | Doi | 10.1053/gast.2002.32991 |
| Citation | Dunker N, et al. (2002) The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa. Gastroenterology 122(5):1364-75 |
| abstractText | BACKGROUND & AIMS: Apoptosis is especially relevant in the gastrointestinal tract because the mammalian intestinal mucosa undergoes continual epithelial regeneration. Most recently, we confirmed the proapoptotic role of endogenous transforming growth factor (TGF)-beta in the developing chick retina as well as in chick ciliary, dorsal root, and spinal motor neurons. In the present study, we determined to establish the role of TGF-beta2 and TGF-beta3 in mediating apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice. METHODS: Intestinal localization of TGF-beta2 and TGF-beta3 isoforms and antiapoptotic molecules Bcl-xL and Bcl-2 was examined immunocytochemically and by Western blot analysis. Apoptosis was detected by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and proliferation was detected by proliferating cell nuclear antigen stains. RESULTS: TGF-beta2 was detected in endocrine cells, whereas TGF-beta3 was predominantly found in goblet cells. Programmed cell death was significantly reduced in the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice. This decrease in apoptosis was accompanied by an increase in villus length; proliferation, however, seemed to remain unchanged. The level of Bcl-xL and Bcl-2 was significantly up-regulated in Tgfbeta2(+/-) and Tgfbeta3(+/-) mice. CONCLUSIONS: Our data show that TGF-beta2 and TGF-beta3 play an important role in mediating apoptosis in the intestinal mucosa and regulating apoptosis-associated proteins Bcl-xL and Bcl-2 in vivo. |
