| 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 |
Related Documents
:
|
9012897 - Nitric oxide and the lung: an overview. 9489517 - Effects of nitroglycerin and sodium nitroprusside on endexpiratory concentrations of ni... 17437657 - Endogenous nitric oxide reduces the efficacy of the endothelin system to maintain blood... 1619907 - Evaluation of endothelium-derived nitric oxide mediated vasodilation utilizing ex vivo ... 8511497 - The significance of probe design in evaluation of colonic perfusion with laser doppler ... 12569277 - Ventricular repolarization is prolonged in nondipper hypertensive patients: role of lef... |
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: 2013-04-16 |
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 |
Affiliation:
|
Dept. of Surgery, College of Human Medicine, Michigan State Univ., Lansing, MI 48912, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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/Flavonoids; 0/PD 98059 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Colitis is associated with a loss of intestinofugal neurons.
Next Document: Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents...