Steinkamp, M and Geerling, I and Seufferlein, T and Von Boyen, G and Egger, B and Grossmann, J and Ludwig, L and Adler, G and Reinshagen, M (2003) Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. GASTROENTEROLOGY, 124 (7). pp. 1748-1757. ISSN 0016-5085,
Full text not available from this repository.Abstract
Background & Aims: Ablation of the enteric glia leads to a fulminant hemorrhagic jejunoileitis. We hypothesized that glial-derived neurotrophic factor (GDNF) may be involved in mucosal protection of the gut. Therefore, we examined the regulation of GDNF and its receptor (GFR-alpha1) in colonic inflammation and its effects on colonic epithelial cell apoptosis. Methods: The expression of GDNF and GFR-alpha1 was investigated in experimental colitis of rats and in human inflammatory bowel disease (IBD)). GDNF-Induced activation of Akt (protein kinase B [PKB]) and mitogen-activated protein kinase (MAPK) in the colonic epithelial cell lines HT-29 and SW480 was studied. Furthermore, the antiapoptotic potency of GDNF in SW480 cells was evaluated. Results: GDNF was specifically up-regulated in experimental rat colitis and in IBD. In contrast, GFR-alpha1 was constitutively expressed in rat and human colonic epithelium. GDNF potently activated MAPK and Akt (PKB) in colonic epithelia[ cells. Moreover, GDNF strongly prevented apoptosis in SW480 cells. Our data show that GDNF-mediated protection against apoptosis depends on activation of the MAPK and phosphatidylinositol 3-kinase/Akt (PKB) pathways. Conclusions. GDNF is up-regulated in IBD and has strong antiapoptotic properties in colonic epithelial cells. This points to a novel role of the neurotrophic factor GDNF for mucosal protection and regeneration in IBD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NERVE GROWTH-FACTOR; MICE LACKING GDNF; ULCERATIVE-COLITIS; PROTEIN-KINASE; CROHNS-DISEASE; NEURONS; ADULT; PERMEABILITY; EXPRESSION; SURVIVAL; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 May 2021 06:30 |
| Last Modified: | 19 May 2021 06:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38928 |
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