Document Detail


Influence of defunctionalization and mechanical forces on intestinal epithelial wound healing.
MedLine Citation:
PMID:  22997197     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The influence on mucosal healing of luminal nutrient flow and the forces it creates are poorly understood. We hypothesized that altered deformation and extracellular pressure mediate, in part, the effects of defunctionalization on mucosal healing. We created patent or partially obstructing defunctionalizing jejunal Roux-en-Y anastomoses in rats to investigate mucosal healing in the absence or presence of luminal nutrient flow and measured luminal pressures to document partial obstruction. We used serosal acetic acid to induce ulcers in the proximal, distal, and defunctionalized intestinal segments. After 3 days, we assessed ulcer area, proliferation, and phosphorylated ERK. In vitro, we measured proliferation and migration in Caco-2 and IEC-6 intestinal epithelial cells subjected to cyclic strain, increased extracellular pressure, or strain and pressure together. Defunctionalization of intestine without obstruction reduced phosphorylated ERK, slowed ulcer healing, and inhibited mucosal proliferation. This outcome was blocked by PD-98059. Partial obstruction delayed ulcer healing but stimulated proliferation independently of ERK. In vitro, strain increased Caco-2 and IEC-6 proliferation and reduced migration across collagen but reduced proliferation and increased migration across fibronectin. In contrast, increased pressure and the combination of pressure and strain increased proliferation and reduced migration independently of substrate. PD-98059 reduced basal migration but increased migration under pressure. These results suggest that loss of the repetitive distension may decrease mucosal healing in defunctionalized bowel, while increased luminal pressure above anastomoses or in spastic bowel disease could further inhibit mucosal healing, despite peristaltic repetitive strain. ERK may mediate the effects of repetitive deformation but not the effects of pressure.
Authors:
Pavlo L Kovalenko; Thomas L Flanigan; Lakshmi Chaturvedi; Marc D Basson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-09-20
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  303     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-01-15     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G1134-43     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anastomosis, Roux-en-Y
Animals
Caco-2 Cells
Cell Movement / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Female
Flavonoids / pharmacology
Humans
Intestinal Mucosa / physiology*
Intestinal Obstruction / physiopathology
Jejunum / injuries
MAP Kinase Signaling System / drug effects,  physiology
Pressure / adverse effects
Rats
Rats, Wistar
Ulcer / therapy
Wound Healing / physiology*
Grant Support
ID/Acronym/Agency:
R01 DK-067257/DK/NIDDK NIH HHS; T32 GM-008420/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Flavonoids
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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