| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Surgery, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201
Early mucosal restitution is a rapid process
by which differentiated intestinal epithelial cells migrate to reseal
superficial wounds. However, most of the in vitro studies for
restitution employ undifferentiated intestinal crypt cells as a model.
The transcription factor, Cdx2, plays an important role in the
regulation of intestinal epithelial differentiation. Forced expression
of the Cdx2 gene in undifferentiated intestinal crypt cells
induces the development of a differentiated phenotype. The current
study was designed to determine changes in differentiated intestinal epithelial cell migration after wounding in the stable
Cdx2-transfected IEC-6 cells and then to examine involvement of
polyamines and nonmuscle myosin II in the process of cell motility.
Cdx2-transfected IEC-6 cells were associated with a highly
differentiated phenotype and exhibited increased cell migration after
wounding. Migration of Cdx2-transfected IEC-6 cells were
approximately four times that of nontransfected IEC-6 cells. Migration
after wounding was associated with significant increases in polyamine
synthesis. Depletion of cellular polyamines by 5 mM
-difluoromethylornithine (DFMO), a specific inhibitor of polyamine
biosynthesis, inhibited cell migration without affecting the
differentiated phenotype. DFMO also decreased levels of nonmuscle
myosin II mRNA and protein and resulted in reorganization of myosin II,
along with a marked reduction in stress fibers. Exogenous spermidine
given together with DFMO not only returned nonmuscle myosin II levels
and cellular distribution toward normal but also restored cell
migration to control levels. These results indicate that 1)
Cdx2-transfected IEC-6 cells exhibit increased cell migration
after wounding and 2) cellular polyamines are absolutely
required for stimulation of cell migration in association with their
ability to modulate the structural organization of nonmuscle myosin II.
Cdx2 gene; restitution; ornithine decarboxylase; cytoskeleton; mucosal injury; differentiation
This article has been cited by other articles:
|
|
 |
|
  J. Chen, J. N. Rao, T. Zou, L. Liu, B. S. Marasa, L. Xiao, X. Zeng, D. J. Turner, and J.-Y. Wang Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G568 - G576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Blikslager, A. J. Moeser, J. L. Gookin, S. L. Jones, and J. Odle Restoration of Barrier Function in Injured Intestinal Mucosa Physiol Rev, April 1, 2007; 87(2): 545 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Rhoads, B. A. Corl, R. Harrell, X. Niu, L. Gatlin, O. Phillips, A. Blikslager, A. Moeser, G. Wu, and J. Odle Intestinal ribosomal p70S6K signaling is increased in piglet rotavirus enteritis Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G913 - G922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Rao, L. Liu, T. Zou, B. S. Marasa, D. Boneva, S. R. Wang, D. L. Malone, D. J. Turner, and J.-Y. Wang Polyamines are required for phospholipase C-{gamma}1 expression promoting intestinal epithelial restitution after wounding Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G335 - G343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Rao, O. Platoshyn, V. A. Golovina, L. Liu, T. Zou, B. S. Marasa, D. J. Turner, J. X.-J. Yuan, and J.-Y. Wang TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G782 - G792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, J. N. Rao, L. Liu, T. Zou, K. M. Keledjian, D. Boneva, B. S. Marasa, and J.-Y. Wang Polyamines are necessary for synthesis and stability of occludin protein in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1159 - G1169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Vaidya, R. M. Ray, and L. R. Johnson MEK1 restores migration of polyamine-depleted cells by retention and activation of Rac1 in the cytoplasm Am J Physiol Cell Physiol, February 1, 2005; 288(2): C350 - C359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, J. N. Rao, L. Liu, T.-T. Zou, D. J. Turner, B. L. Bass, and J.-Y. Wang Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1174 - C1187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Rao, X. Guo, L. Liu, T. Zou, K. S. Murthy, J. X.-J. Yuan, and J.-Y. Wang Polyamines regulate Rho-kinase and myosin phosphorylation during intestinal epithelial restitution Am J Physiol Cell Physiol, April 1, 2003; 284(4): C848 - C859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, J. N. Rao, L. Liu, M. Rizvi, D. J. Turner, and J.-Y. Wang Polyamines regulate beta -catenin tyrosine phosphorylation via Ca2+ during intestinal epithelial cell migration Am J Physiol Cell Physiol, September 1, 2002; 283(3): C722 - C734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Rao, O. Platoshyn, L. Li, X. Guo, V. A. Golovina, J. X.-J. Yuan, and J.-Y. Wang Activation of K+ channels and increased migration of differentiated intestinal epithelial cells after wounding Am J Physiol Cell Physiol, April 1, 2002; 282(4): C885 - C898. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
