title: Larazotide acetate promotes tight junction assembly in epithelial cells.
abstract: 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 "leaky" 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.
authors.affiliation: Alba Therapeutics, 650 S. Exeter, Suite 1040, 10th floor, Baltimore, MD 21202, United States.
authors.forename: Shobha
authors.initials: S
authors.lastname: Gopalakrishnan
authors.forename: Amit
authors.initials: A
authors.lastname: Tripathi
authors.forename: Amir P
authors.initials: AP
authors.lastname: Tamiz
authors.forename: Sefik S
authors.initials: SS
authors.lastname: Alkan
authors.forename: Niranjan B
authors.initials: NB
authors.lastname: Pandey
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D009842:Oligopeptides / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D000199:Actins; D015820:Cadherins; D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D009842:Oligopeptides; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C525167:larazotide acetate; D002118:Calcium