| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print March 30, 2004
Pediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213
Corresponding Author: david.hackam{at}chp.edu
Diseases of gut inflammation such as neonatal necrotizing enterocolitis (NEC) result after an injury to the mucosal lining of the intestine, leading to translocation of bacteria and endotoxin (lipopolysaccharide, LPS). Intestinal mucosal defects are repaired by the process of intestinal restitution, during which enterocytes migrate from healthy areas to sites of injury. In an animal model of NEC, we determined that intestinal restitution was significantly impaired compared to control animals. We therefore sought to determine the mechanisms governing enterocyte migration under basal conditions and after an endotoxin challenge. Here we show that the cytoskeletal reorganization and stress fiber formation required for migration in IEC-6 enterocytes requires RhoA. Enterocytes were found to express the endotoxin receptor toll like receptor 4 (TLR4), which served to bind and internalize lipopolysaccharide. Strikingly, endotoxin treatment significantly inhibited intestinal restitution, as measured by impaired IEC-6 cell migration across a scraped wound. LPS was found to increase RhoA activity in a PI3K-dependent manner, leading to an increase in phosphorylation of focal adhesion kinase and an enhanced number of focal adhesions. Importantly, endotoxin caused a progressive, RhoA-dependent increase in cell-matrix tension/contractility which correlated with the observed impairment in enterocyte migration. We therefore conclude that endotoxin inhibits enterocyte migration through a RhoA-dependent increase in focal adhesions and enhanced cell adhesiveness, which may participate in the impaired restitution observed in experimental NEC.
J. Biol. Chem, 10.1074/jbc.M313620200
Submitted on December 12, 2003
Revised on March 30, 2004
Accepted on March 29, 2004
Endotoxin inhibits Intestinal epithelial restitution through activation of Rho-GTPase and increased focal adhesions
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Sodhi, W. Richardson, S. Gribar, and D. J. Hackam The development of animal models for the study of necrotizing enterocolitis Dis. Model. Mech., September 1, 2008; 1(2-3): 94 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Leaphart, S. Dai, S. C. Gribar, W. Richardson, J. Ozolek, X.-h. Shi, J. R. Bruns, M. Branca, J. Li, O. A. Weisz, et al. Interferon-{gamma} inhibits enterocyte migration by reversibly displacing connexin43 from lipid rafts Am J Physiol Gastrointest Liver Physiol, September 1, 2008; 295(3): G559 - G569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Gribar, R. J. Anand, C. P. Sodhi, and D. J. Hackam The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation J. Leukoc. Biol., March 1, 2008; 83(3): 493 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Anand, S. Dai, C. Rippel, C. Leaphart, F. Qureshi, S. C. Gribar, J. W. Kohler, J. Li, D. B. Stolz, C. Sodhi, et al. Activated macrophages inhibit enterocyte gap junctions via the release of nitric oxide Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G109 - G119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Mi, D. Swigon, B. Riviere, S. Cetin, Y. Vodovotz, and D. J. Hackam One-Dimensional Elastic Continuum Model of Enterocyte Layer Migration Biophys. J., December 1, 2007; 93(11): 3745 - 3752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Leaphart, J. Cavallo, S. C. Gribar, S. Cetin, J. Li, M. F. Branca, T. D. Dubowski, C. P. Sodhi, and D. J. Hackam A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair J. Immunol., October 1, 2007; 179(7): 4808 - 4820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Levy, K. P. Mollen, J. M. Prince, D. J. Kaczorowski, R. Vallabhaneni, S. Liu, K. J. Tracey, M. T. Lotze, D. J. Hackam, M. P. Fink, et al. Systemic inflammation and remote organ injury following trauma require HMGB1 Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1538 - R1544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Voltan, I. Castagliuolo, M. Elli, S. Longo, P. Brun, R. D'Inca, A. Porzionato, V. Macchi, G. Palu, G. C. Sturniolo, et al. Aggregating Phenotype in Lactobacillus crispatus Determines Intestinal Colonization and TLR2 and TLR4 Modulation in Murine Colonic Mucosa Clin. Vaccine Immunol., September 1, 2007; 14(9): 1138 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cetin, C. L. Leaphart, J. Li, I. Ischenko, M. Hayman, J. Upperman, R. Zamora, S. Watkins, H. R. Ford, J. Wang, et al. Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1347 - G1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Neal, C. Leaphart, R. Levy, J. Prince, T. R. Billiar, S. Watkins, J. Li, S. Cetin, H. Ford, A. Schreiber, et al. Enterocyte TLR4 Mediates Phagocytosis and Translocation of Bacteria Across the Intestinal Barrier. J. Immunol., March 1, 2006; 176(5): 3070 - 3079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chanchevalap, M. O. Nandan, B. B. McConnell, L. Charrier, D. Merlin, J. P. Katz, and V. W. Yang Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells Nucleic Acids Res., February 25, 2006; 34(4): 1216 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Grishin, J. Wang, D. A. Potoka, D. J. Hackam, J. S. Upperman, P. Boyle, R. Zamora, and H. R. Ford Lipopolysaccharide Induces Cyclooxygenase-2 in Intestinal Epithelium via a Noncanonical p38 MAPK Pathway J. Immunol., January 1, 2006; 176(1): 580 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Hildebrand Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network J. Cell Sci., November 15, 2005; 118(22): 5191 - 5203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Cario BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2 Gut, August 1, 2005; 54(8): 1182 - 1193. [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. McHardy, K. Warabi, R. J. Andersen, C. D. Roskelley, and M. Roberge Strongylophorine-26, a Rho-dependent inhibitor of tumor cell invasion that reduces actin stress fibers and induces nonpolarized lamellipodial extensions Mol. Cancer Ther., May 1, 2005; 4(5): 772 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Abreu, M. Fukata, and M. Arditi TLR Signaling in the Gut in Health and Disease J. Immunol., April 15, 2005; 174(8): 4453 - 4460. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
