Clinical-alimentary tractGlial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells☆
Section snippets
Antibodies and reagents
Antibodies used in this study were as follows: p42/44 mitogen-activated protein kinase (MAPK) and Akt (protein kinase B [PKB]) (Cell Signaling Technology, Beverly, MA), GDNF receptor (GFR)-α1 antibody (Transduction Labs/Becton Dickinson, Heidelberg, Germany), GDNF antibodies (R & D Systems, Wiesbaden, Germany; Santa Cruz Biotechnology, Heidelberg, Germany), cleaved poly(ADP-ribose)polymerase (PARP) antibody (Biosource, Camarillo, CA), β -actin antibody (Dr. Andre Menke, University of Ulm), and
GDNF and GFR-α1 in normal and inflamed rat colonic epithelium
In colonic tissue sections of control rats, a minor GDNF immunoreactivity could be detected at the surface epithelium of the colonic mucosa (Figure 1A) One and 3 days after induction of colitis, we observed a stronger GDNF staining at the colonic epithelium reaching more toward the crypt base compared with controls (Figure 1B and C). At day 21, the epithelial GDNF staining had decreased to the basal level (Figure 1D). As shown in Figure 1E, the myenteric plexus of rats was also GDNF positive.
Discussion
In this report, we show that GDNF is up-regulated in IBD and experimental colitis and that this neurotrophic factor has strong antiapoptotic effects on colonic epithelial cells. Our data strongly suggest a novel endogenous regulatory function of GDNF in the protection of the epithelial lining during mucosal inflammation.
The expression of GDNF in the gut is crucial for the neuronal development of the gut. Mice lacking GDNF or its receptor, GFR-α, among other defects, fail to develop an intact
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2023, Neuroscience LettersRole of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis
2023, Ageing Research ReviewsCitation Excerpt :The protective effect of S-nitrosoglutathione (GSNO), a bioavailable source of NO, is from the prevention of bacterial invasion in intestinal epithelial cells, however, its high concentration might induce barrier damage, as it acts as a NO donor (Dijkstra et al., 2004), as demonstrated in Fig. 2. Glia also shows the release of barrier-enhancing factors in vitro, like glial-cell-derived neurotrophic factor (GDNF), also present in the smooth muscle, which prevents TNF-induced intestinal epithelial cell death and promotes neurogenesis and neuron survival (Steinkamp et al., 2003). However, recent findings indicate that mice can tolerate a large loss of enteric glia, decreasing the notion of the crucial role of the enteric glial cells for IEB homeostasis.
Glial cell line-derived neurotrophic factor ameliorates dextran sulfate sodium-induced colitis in mice via a macrophage-mediated pathway
2021, International ImmunopharmacologyCitation Excerpt :Studies showed that the expression of GDNF was elevated in intestinal tissues from experimental models or patients with functional dyspepsia,[19] irritable bowel syndrome[20,21] and acute intestinal ischemia reperfusion injury. [22] Similarly, early studies reported an increase of GDNF in colon samples from patients with IBD. [23,24] However, a more recent study by analyzing the whole gut wall from 18 patients revealed that GDNF was significantly reduced in colon of patients with CD and UC, and Meir et al. speculated that GDNF expression might be influenced by the state of inflammation and was dynamic in the course of IBD.[11]
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Supported by Deutsche Forschungsgemeinschaft, no. Re/789/2-5.