Larazotide acetate promotes tight junction assembly in epithelial cells

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• 作者：Shobha Gopalakrishnan ; Amit Tripathi¹ ; Amir P. Tamiz ; Sefik S. Alkan² ; Niranjan B. Pandey ; ^{pandey.niranjan@gmail.com}
• 关键词：TJ ; tight junction ; AJ ; adherens junction ; LY ; Lucifer Yellow ; HCM ; high calcium medium ; NCM ; no calcium medium
• 刊名：Peptides
• 出版年：2012
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：May, 2012
• 卷：35
• 期：1
• 页码：95-101
• 文件大小：928 K

摘要

Tight junctions (TJ) control paracellular permeability and apical-basolateral polarity of epithelial cells. Dysregulated permeability is associated with pathological conditions, such as celiac disease and inflammatory bowel disease. TJ formation is dependent on E-cadherin-mediated cell-cell adhesion and actin rearrangement, and is regulated by the Rho family GTPase and aPKC signaling pathways. Larazotide acetate, an 8-mer peptide and TJ modulator, inhibits TJ disassembly and dysfunction caused by endogenous and exogenous stimuli in intestinal epithelial cells. Here, we examined the effect of larazotide acetate on de novo TJ assembly using 2 different model systems. In MDCK cells, larazotide acetate promoted TJ assembly in a calcium switch assay. Larazotide acetate also promoted actin rearrangement, and junctional distribution of zonula occludens-1 (ZO-1), occludin, claudins, and E-cadherin. Larazotide acetate promoted TJ maturation and decreased paracellular permeability in 鈥渓eaky鈥?Caco-2 cells. Taken together, our data indicate that larazotide acetate enhances TJ assembly and barrier function by promoting actin rearrangement and redistribution of TJ and AJ proteins.