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Intestinal smooth muscle phenotype determines enteric neuronal survival via GDNF expression.
- Source :
-
Neuroscience [Neuroscience] 2015 Apr 02; Vol. 290, pp. 357-68. Date of Electronic Publication: 2015 Feb 02. - Publication Year :
- 2015
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Abstract
- Intestinal inflammation causes initial axonal degeneration and neuronal death, as well as the proliferation of intestinal smooth muscle cells (ISMC), but subsequent axonal outgrowth leads to re-innervation. We recently showed that expression of glial cell-derived neurotrophic factor (GDNF), the critical neurotrophin for the post-natal enteric nervous system (ENS) is upregulated in ISMC by inflammatory cytokines, leading us to explore the relationship between ISMC growth and GDNF expression. In co-cultures of myenteric neurons and ISMC, GDNF or fetal calf serum (FCS) was equally effective in supporting neuronal survival, with neurons forming extensive axonal networks among the ISMC. However, only GDNF was effective in low-density cultures where neurons lacked contact with ISMC. In early-passage cultures of colonic circular smooth muscle cells (CSMC), polymerase chain reaction (PCR) and western blotting showed that proliferation was associated with expression of GDNF, and the successful survival of neonatal neurons co-cultured on CSMC was blocked by vandetanib or siGDNF. In tri-nitrobenzene sulfonic acid (TNBS)-induced colitis, immunocytochemistry showed the selective expression of GDNF in proliferating CSMC, suggesting that smooth muscle proliferation supports the ENS in vivo as well as in vitro. However, high-passage CSMC expressed significantly less GDNF and failed to support neuronal survival, while expressing reduced amounts of smooth muscle marker proteins. We conclude that in the inflamed intestine, smooth muscle proliferation supports the ENS, and thus its own re-innervation, by expression of GDNF. In chronic inflammation, a compromised smooth muscle phenotype may lead to progressive neural damage. Intestinal stricture formation in human disease, such as inflammatory bowel disease (IBD), may be an endpoint of failure of this homeostatic mechanism.<br /> (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Axons drug effects
Axons physiology
Cattle
Cell Proliferation physiology
Cell Survival drug effects
Coculture Techniques
Colitis physiopathology
Enteric Nervous System drug effects
Glial Cell Line-Derived Neurotrophic Factor antagonists & inhibitors
Intestines drug effects
Intestines immunology
Male
Mice, Inbred BALB C
Muscle, Smooth drug effects
Neurons drug effects
Rats, Sprague-Dawley
Trinitrobenzenesulfonic Acid
Cell Survival physiology
Enteric Nervous System physiology
Glial Cell Line-Derived Neurotrophic Factor metabolism
Intestines physiology
Muscle, Smooth physiology
Neurons physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 290
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 25655216
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2015.01.056