Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells
M Steinkamp, I Geerling, T Seufferlein, G Von Boyen… - Gastroenterology, 2003 - Elsevier
M Steinkamp, I Geerling, T Seufferlein, G Von Boyen, B Egger, J Grossmann, L Ludwig…
Gastroenterology, 2003•ElsevierBACKGROUND & 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-α1) in colonic inflammation and its effects on colonic epithelial cell apoptosis.
METHODS:: The expression of GDNF and GFR-α1 was investigated in experimental colitis
of rats and in human inflammatory bowel disease (IBD). GDNF-induced activation of Akt …
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-α1) in colonic inflammation and its effects on colonic epithelial cell apoptosis.
METHODS:: The expression of GDNF and GFR-α1 was investigated in experimental colitis
of rats and in human inflammatory bowel disease (IBD). GDNF-induced activation of Akt …
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-α1) in colonic inflammation and its effects on colonic epithelial cell apoptosis.
METHODS
The expression of GDNF and GFR-α1 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-α1 was constitutively expressed in rat and human colonic epithelium. GDNF potently activated MAPK and Akt (PKB) in colonic epithelial 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.
Elsevier