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.

scholarly journals The effects of glutamine on intestinal epithelial cell proliferation in parenterally fed rats

Gut ◽  
1999 ◽  
Vol 44 (5) ◽  
pp. 608-614 ◽  
Author(s):  
N Mandir ◽  
R A Goodlad
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Epithelial Cell ◽  
Mitotic Activity ◽  
Intestinal Epithelial Cell ◽  
Distribution Curve ◽  
Treated Group ◽  
Growth Fraction ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation

BACKGROUNDSeveral papers have indicated that glutamine is a preferred fuel for the enterocyte and that it can increase intestinal epithelial cell proliferation.AIMSTo investigate the effects of glutamine on intestinal epithelial cell proliferation in the parenterally fed rat.METHODSFive groups of six rats were fed parenterally; a group of orally fed rats was also studied. Crypt cell proliferation was studied after six days using native mitoses in microdissected crypts and bromodeoxyuridine labelling.RESULTSNo effect of treatment was seen on intestinal weight; however, the weights of the small intestine, caecum, and colon were all significantly heavier in the orally fed group than in the total parenteral nutrition groups (p<0.001). There was no effect of any of the glutamine treatments on mitotic activity in the small intestine. In the colon there was a small increase in native mitoses with glutamine (p=0.03). There was also an indication of increased proliferative activity in the first fifth of the small intestine and colon with glutamine. Little effect of glutamine on bromodeoxyuridine labelling in either site was observed, but there was a small but significant reduction in growth fraction of the colon of the glutamine treated group. The labelling distribution curve from sections and the mitotic distribution curve obtained from crypt squashes showed a good correlation.CONCLUSIONGlutamine has a small, but significant effect on mitotic activity but only in the colon. Modest effects on the distribution of labelled cells were also seen.

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.

scholarly journals A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

2021 ◽  
Vol 17 (5) ◽  
pp. e1009598
Author(s):  
Chengcheng Liu ◽  
Kendall Stocke ◽  
Zackary R. Fitzsimonds ◽  
Lan Yakoumatos ◽  
Daniel P. Miller ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tyrosine Phosphatase ◽  
Periodontal Pathogen ◽  
Tyrosine Phosphatases ◽  
Mesenchymal Transition ◽  
Gingival Epithelial Cells ◽  
Epithelial Cell Migration

Tyrosine phosphatases are often weaponized by bacteria colonizing mucosal barriers to manipulate host cell signal transduction pathways. Porphyromonas gingivalis is a periodontal pathogen and emerging oncopathogen which interferes with gingival epithelial cell proliferation and migration, and induces a partial epithelial mesenchymal transition. P. gingivalis produces two tyrosine phosphatases, and we show here that the low molecular weight tyrosine phosphatase, Ltp1, is secreted within gingival epithelial cells and translocates to the nucleus. An ltp1 mutant of P. gingivalis showed a diminished ability to induce epithelial cell migration and proliferation. Ltp1 was also required for the transcriptional upregulation of Regulator of Growth and Cell Cycle (RGCC), one of the most differentially expressed genes in epithelial cells resulting from P. gingivalis infection. A phosphoarray and siRNA showed that P. gingivalis controlled RGCC expression through Akt, which was activated by phosphorylation on S473. Akt activation is opposed by PTEN, and P. gingivalis decreased the amount of PTEN in epithelial cells. Ectopically expressed Ltp1 bound to PTEN, and reduced phosphorylation of PTEN at Y336 which controls proteasomal degradation. Ltp-1 induced loss of PTEN stability was prevented by chemical inhibition of the proteosome. Knockdown of RGCC suppressed upregulation of Zeb2 and mesenchymal markers by P. gingivalis. RGCC inhibition was also accompanied by a reduction in production of the proinflammatory cytokine IL-6 in response to P. gingivalis. Elevated IL-6 levels can contribute to periodontal destruction, and the ltp1 mutant of P. gingivalis incited less bone loss compared to the parental strain in a murine model of periodontal disease. These results show that P. gingivalis can deliver Ltp1 within gingival epithelial cells, and establish PTEN as the target for Ltp1 phosphatase activity. Disruption of the Akt1/RGCC signaling axis by Ltp1 facilitates P. gingivalis-induced increases in epithelial cell migration, proliferation, EMT and inflammatory cytokine production.

scholarly journals Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation

2015 ◽  
Vol 226 (3) ◽  
pp. 135-143 ◽  
Author(s):  
Tatiana Dorfman ◽  
Yulia Pollak ◽  
Rima Sohotnik ◽  
Arnold G Coran ◽  
Jacob Bejar ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Real Time ◽  
Real Time Pcr ◽  
Intestinal Epithelial Cell ◽  
Diabetic Rats ◽  
Male Rats ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation

The Wnt/β-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, and cell survival of the gastrointestinal epithelium. Recent evidence indicates that the Wnt/β-catenin pathway is activated under diabetic conditions. The purpose of this study was to evaluate the role of Wnt/β-catenin signaling during diabetes-induced enteropathy in a rat model. Male rats were divided into three groups: control rats received injections of vehicle; diabetic rats received injections of one dose of streptozotocin (STZ); and diabetic–insulin rats received injections of STZ and were treated with insulin given subcutaneously at a dose of 1 U/kg twice daily. Rats were killed on day 7. Wnt/β-catenin-related genes and expression of proteins was determined using real-time PCR, western blotting, and immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes were upregulated in diabetic rats compared with control animals including the target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in β-catenin protein compared with control animals. Treatment of diabetic rats attenuated the stimulating effect of diabetes on intestinal cell proliferation and Wnt/β-catenin signaling. In conclusion, enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation.

scholarly journals c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation

2011 ◽  
Vol 301 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
Justine Elliott ◽  
Nadezhda N. Zheleznova ◽  
Patricia D. Wilson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Collecting Duct ◽  
Specific Inhibitor ◽  
Cell Phenotype ◽  
Epithelial Cell Proliferation ◽  
Matrix Adhesion ◽  
Cyst Lining

c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY418)-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY418-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α2β1-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.

scholarly journals Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro

1999 ◽  
Vol 80 (10) ◽  
pp. 1550-1557 ◽  
Author(s):  
C Booth ◽  
D F Hargreaves ◽  
J A Hadfield ◽  
A T McGown ◽  
C S Potten
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation
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