Human submucosal neurones regulate intestinal epithelial cell proliferation: evidence from a novel co-culture model.
The role of the human enteric nervous system (ENS) in the control of the intestinal epithelium organization and proliferation is unknown. To address this issue, we developed a novel co-culture model, consisting of human submucosa containing the submucosal plexus and a human colonic epithelial monolayer. After 3 days in basal conditions (i.e. in absence of neuronal activation) epithelium disorganization and proliferation occurred. In contrast, electrical activation of submucosal neurones maintained monolayer organization and decreased cell proliferation. These effects were blocked by tetrodotoxin and a vasoactive intestinal peptide (VIP) receptor antagonist, and reproduced by VIP. In conclusion, our study suggests that the human ENS is involved in the control of epithelial cell proliferation.
Toumi
F
F
INSERM U539, Faculté de Médecine, Nantes, France.
Neunlist
M
M
Cassagnau
E
E
Parois
S
S
Laboisse
C L
CL
Galmiche
J-P
JP
Jarry
A
A
D000368:Aged; D000779:Anesthetics, Local / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D003106:Colon / Q000166:cytology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D013368:Submucous Plexus / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000779:Anesthetics, Local; D005765:Gastrointestinal Agents; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin