GDNF protects enteric glia from apoptosis: evidence for an autocrine loop

BMC Gastroenterology

Georg BT von Boyen²  Eugen Zizer²  Carolin Pflueger²  Ulrike Spaniol²  Nadine Schulte²  Heike Gundel²  Martin Steinkamp¹ 

[1] Department of Gastroenterology, Endocrinology and Metabolism, University of Gießen und Marburg GmbH, Site Marburg, Baldingerstraße, 35037 Marburg, Germany;Department of Internal Medicine I (Gastroenterology), University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany

关键词: apoptosis;    IBD;    Crohn's disease;    GDNF;    enteric glia;   

Others  :  1113152
DOI  :  10.1186/1471-230X-12-6

 received in 2011-05-13, accepted in 2012-01-17,  发布年份 2012

【 摘 要 】

Background

Enteric glia cells (EGC) play an important role in the maintenance of intestinal mucosa integrity. During the course of acute Crohn's disease (CD), mucosal EGC progressively undergo apoptosis, though the mechanisms are largely unknown. We investigated the role of Glial-derived neurotrophic factor (GDNF) in the regulation of EGC apoptosis.

Methods

GDNF expression and EGC apoptosis were determined by immunofluorescence using specimen from CD patients. In primary rat EGC cultures, GDNF receptors were assessed by western blot and indirect immunofluorescence microscopy. Apoptosis in cultured EGC was induced by TNF-α and IFN-γ, and the influence of GDNF on apoptosis was measured upon addition of GDNF or neutralizing anti-GDNF antibody.

Results

Increased GDNF expression and Caspase 3/7 activities were detected in in specimen of CD patients but not in healthy controls. Moreover, inactivation of GDNF sensitized in EGC cell to IFN-γ/TNF-α induced apoptosis.

Conclusions

This study proposes the existence of an autocrine anti-apoptotic loop in EGC cells which is operative in Crohn's disease and dependent of GDNF. Alterations in this novel EGC self-protecting mechanism could lead to a higher susceptibility towards apoptosis and thus contribute to disruption of the mucosal integrity and severity of inflammation in CD.

【 授权许可】

   
2012 Steinkamp et al; licensee BioMed Central Ltd.

【 图 表 】

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