p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Whitney G. Smalley-Freed et al . J Clin Invest. 120. 1824–1835 (2010)

Speaker: Chia-Lun Tsai(蔡佳倫)                           Time: 14:10-15:00, May 18, 2011

Commentator: Dr. Jyh-Wei Shin (辛致煒老師)    Place: Room 601

Abstract

The main role of epithelial-cadherin (E-cadherin) is widely regarded as a master organizer and a classic tumor suppressor of the epithelial phenotype because it frequent down regulation in advanced tumors and plays a causal role in the transition to tumor metastasis . p120-catenin (referred to herein as p120) directly regulates cadherin stability. In the previous studies suggest cadherin plays important role  in inflammatory bowel diseases (IBD e.g., Crohn disease, ulcerative colitis), which are chronically remitting inflammatory conditions of intestinal homeostatsis and, by inference, may also related to  p120. The result showed p120 KO mice died between 11 and 23 days (average = 17 days) after birth, and the small intestine of p120 KO mice was pale white due to loss of blood, and its weight on average about half as controls, then the small intestine or colon from p120 KO or control mice were analyzed by H&E staining which was found that rapid deterioration of gut morphology. To further characterize the phenotypical defects of p120 KO mice, that intercellular gaps were also visible in the p120 KO colon immediately after birth (day 0). E-cadherin levels were selectively decreased in p120-null cells, as compared with cells that retained p120 expression. As expected, β-catenin and α-catenin levels decreased in parallel with those of E-cadherin, that p120 ablation selectively downregulates the E-cadherin complex, but the desmoglein and occludin are not affected by p120 loss. The atypical COX-2(an enzyme associated with IBD) expressing neutrophils in p120-null areas.To know the role of p120 in the tight junction between cells, they used p120 KD in HCA7 cells to abolishes barrier function and increased neutrophil attachment bytransepithelial electrical resistance (TER).In summary,  the authors show in this study that p120 has an essential role in barrier function and epithelial homeostasis and survival in the intestine.

References

1.     Hermiston ML et al .Inf lammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science. 270(5239):1203–1207.(1995)