Involvement of tumor necrosis factor αin intestinal epithelial cell proliferation following paneth cell destruction

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.

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Tumor necrosis factor-α represses the expression of NHE2 through NF-κB activation in intestinal epithelial cell model, C2BBe1

Inflammatory Bowel Diseases ◽

10.1002/ibd.21419 ◽

2011 ◽

Vol 17 (3) ◽

pp. 720-731 ◽

Cited By ~ 16

Author(s):

Ruhul Amin ◽

Temitope Orenuga ◽

Sangeeta Tyagi ◽

Pradeep K. Dudeja ◽

Krishnamurthy Ramaswamy ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Epithelial Cell ◽

Tumor Necrosis ◽

Intestinal Epithelial Cell ◽

Tumor Necrosis Factor Α ◽

Cell Model ◽

Intestinal Epithelial ◽

Factor Α ◽

Necrosis Factor

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

Journal of Endocrinology ◽

10.1530/joe-14-0725 ◽

2015 ◽

Vol 226 (3) ◽

pp. 135-143 ◽

Cited By ~ 9

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.

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