Polyamines regulate β-catenin tyrosine phosphorylation via Ca2+ during intestinal epithelial cell migration

2002 ◽  
Vol 283 (3) ◽  
pp. C722-C734 ◽  
Author(s):  
Xin Guo ◽  
Jaladanki N. Rao ◽  
Lan Liu ◽  
Mort Rizvi ◽  
Douglas J. Turner ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Kinase Inhibitor ◽  
Intestinal Epithelial Cells ◽  
Critical Role ◽  
Cytoskeletal Proteins ◽  
Intestinal Epithelial ◽  
Epithelial Cell Migration

Polyamines are essential for early mucosal restitution that occurs by epithelial cell migration to reseal superficial wounds after injury. Normal intestinal epithelial cells are tightly bound in sheets, but they need to be rapidly disassembled during restitution. β-Catenin is involved in cell-cell adhesion, and its tyrosine phosphorylation causes disassembly of adhesion junctions, enhancing the spreading of cells. The current study determined whether polyamines are required for the stimulation of epithelial cell migration by altering β-catenin tyrosine phosphorylation. Migration of intestinal epithelial cells (IEC-6 line) after wounding was associated with an increase in β-catenin tyrosine phosphorylation, which decreased the binding activity of β-catenin to α-catenin. Polyamine depletion by α-difluoromethylornithine reduced cytoplasmic free Ca2+concentration ([Ca2+]cyt), prevented induction of β-catenin phosphorylation, and decreased cell migration. Elevation of [Ca2+]cyt induced by the Ca2+ ionophore ionomycin restored β-catenin phosphorylation and promoted migration in polyamine-deficient cells. Decreased β-catenin phosphorylation through the tyrosine kinase inhibitor herbimycin-A or genistein blocked cell migration, which was accompanied by reorganization of cytoskeletal proteins. These results indicate that β-catenin tyrosine phosphorylation plays a critical role in polyamine-dependent cell migration and that polyamines induce β-catenin tyrosine phosphorylation at least partially through [Ca2+]cyt.

TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding

2006 ◽  
Vol 290 (4) ◽  
pp. G782-G792 ◽  
Author(s):  
Jaladanki N. Rao ◽  
Oleksandr Platoshyn ◽  
Vera A. Golovina ◽  
Lan Liu ◽  
Tongtong Zou ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Transient Receptor Potential ◽  
Intestinal Epithelial Cells ◽  
Critical Role ◽  
Receptor Potential ◽  
Mucosal Injury ◽  
Intestinal Epithelial ◽  
Epithelial Restitution ◽  
Transient Receptor

An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) results from Ca2+ release from intracellular stores and extracellular Ca2+ influx through Ca2+-permeable ion channels and is crucial for initiating intestinal epithelial restitution to reseal superficial wounds after mucosal injury. Capacitative Ca2+ entry (CCE) induced by Ca2+ store depletion represents a major Ca2+ influx mechanism, but the exact molecular components constituting this process remain elusive. This study determined whether canonical transient receptor potential (TRPC)1 served as a candidate protein for Ca2+-permeable channels mediating CCE in intestinal epithelial cells and played an important role in early epithelial restitution. Normal intestinal epithelial cells (the IEC-6 cell line) expressed TRPC1 and TPRC5 and displayed typical records of whole cell store-operated Ca2+ currents and CCE generated by Ca2+ influx after depletion of intracellular stores. Induced TRPC1 expression by stable transfection with the TRPC1 gene increased CCE and enhanced cell migration during restitution. Differentiated IEC-Cdx2L1 cells induced by forced expression of the Cdx2 gene highly expressed endogenous TRPC1 and TRPC5 and exhibited increased CCE and cell migration. Inhibition of TRPC1 expression by small interfering RNA specially targeting TRPC1 not only reduced CCE but also inhibited cell migration after wounding. These findings strongly suggest that TRPC1 functions as store-operated Ca2+ channels and plays a critical role in intestinal epithelial restitution by regulating CCE and intracellular [Ca2+]cyt.

Tumor necrosis factor regulates intestinal epithelial cell migration by receptor-dependent mechanisms

2003 ◽  
Vol 284 (4) ◽  
pp. C953-C961 ◽  
Author(s):  
Julissa Corredor ◽  
Fang Yan ◽  
Christopher C. Shen ◽  
Wei Tong ◽  
Sutha K. John ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Necrosis Factor ◽  
Epithelial Cell ◽  
Tumor Necrosis ◽  
Intestinal Epithelial Cell ◽  
Wound Closure ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Epithelial Cell Migration ◽  
Necrosis Factor

Altered mucosal integrity and increased cytokine production, including tumor necrosis factor (TNF), are the hallmarks of inflammatory bowel disease (IBD). In this study, we addressed the role of TNF receptors (TNFR) on intestinal epithelial cell migration in an in vitro wound closure model. With mouse TNFR1 or TNFR2 knockout intestinal epithelial cells, gene transfection, and pharmacological inhibitors, we show a concentration-dependent receptor-mediated regulation of intestinal cell migration by TNF. A physiological TNF level (1 ng/ml) enhances migration through TNFR2, whereas a pathological level (100 ng/ml) inhibits wound closure through TNFR1. Increased rate of wound closure by TNFR2 or inhibition by TNFR1 cannot be explained by either increased proliferation or apoptosis, respectively. Furthermore, inhibiting Src tyrosine kinase decreases TNF-induced focal adhesion kinase (FAK) tyrosine phosphorylation and cellular migration. We therefore conclude that TNFR2 activates a novel Src-regulated pathway involving FAK tyrosine phosphorylation that enhances migration of intestinal epithelial cells.

scholarly journals Proliferation, not apoptosis, alters epithelial cell migration in small intestine of CFTR null mice

2001 ◽  
Vol 281 (3) ◽  
pp. G681-G687 ◽  
Author(s):  
Ann Marie Gallagher ◽  
Roberta A. Gottlieb
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Intestinal Epithelial ◽  
Transmembrane Conductance Regulator ◽  
Epithelial Cell Proliferation ◽  
Transmembrane Conductance ◽  
Epithelial Cell Migration

Expression of a mutated cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to enhance proliferation within CF airways, and cells expressing a mutated CFTR have been shown to be less susceptible to apoptosis. Because the CFTR is expressed in the epithelial cells lining the gastrointestinal tract and all CF mouse models are characterized by gastrointestinal obstruction, we hypothesized that CFTR null mice would have increased epithelial cell proliferation and reduced apoptosis within the small intestine. The rate of intestinal epithelial cell migration from crypt to villus was increased in CFTR null mice relative to mice expressing the wild-type CFTR. This difference in migration could be explained by an increase in epithelial cell proliferation but not by a difference in apoptosis within the crypts of Lieberkühn. In addition, using two independent sets of CF cell lines, we found that epithelial cell susceptibility to apoptosis was unrelated to the presence of a functional CFTR. Thus increased proliferation but not alterations in apoptosis within epithelial cells might contribute to the pathophysiology of CF.

Sign in / Sign up

Export Citation Format

Share Document