Faculty Opinions recommendation of LSR defines cell corners for tricellular tight junction formation in epithelial cells.

2011 ◽  
Author(s):  
Asma Nusrat ◽  
Stefan Koch
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junction Formation ◽  
Junction Formation

scholarly journals P059 GB004 drives protective effects on immune cells and epithelial cells using human ex vivo monolayer and co-culture systems

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S165-S166
Author(s):  
K Taylor Meadows ◽  
S Murphy ◽  
B G Levesque ◽  
L L Carter ◽  
L Salter-Cid
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Tight Junction ◽  
Immune Cells ◽  
Target Genes ◽  
Protective Effects ◽  
Barrier Integrity ◽  
Culture Systems ◽  
Tight Junction Formation ◽  
Junction Formation

Abstract Background GB004 is a small molecule that stabilizes hypoxia inducible factor (HIF-1α), a key transcription factor involved in the cellular responses at the intersection of hypoxia and inflammation. GB004 induction of HIF-1a target genes improves barrier integrity and reduces barrier permeability in rodent models of colitis. Here we investigated gene expression and secretion of soluble factors elicited by GB004 treatment on immune cells and epithelial cells, human monolayer assays and immune co-culture studies to further explore its protective mechanism. Methods In the BioMAP human co-culture assay, cells were treated with GB004 one hour prior to stimulation and incubated for 24–168 hours. Biomarkers, cell viability and proliferation were assessed. Repligut human stem-cell-derived monolayer platforms were used to assess GB004 effects under unstimulated or TNFa stimulation conditions. Barrier integrity was assessed by Transepithelial Endothelial Electric Resistance (TEER), HIF-1a target genes were assessed in cell lysates, and tight junction formation and epithelial monolayer viability were investigated by immunofluorescence staining. Results GB004 demonstrated activity in 11 of 12 systems in the BioMAP human co-culture assay, which covers a range of disease-relevant immune and non-immune mechanisms under stimulation conditions. Collectively, GB004 treatment led to changes in biomarkers associated with inflammation (sTNFa, IL-8, MCP-1, CXCL11), immunomodulation (sIL-17F, sIL-17A), and tissue remodeling (collagen I, collagen IV). GB004 treatment also reduced the proliferative activity in the in vitro lymphocyte assay systems. In the human Repligut intestinal epithelium assay, GB004 significantly reduced cell death and improved barrier integrity in response to pro-inflammatory cytokines. The protective role of GB004 on barrier integrity was further supported by immunostaining experiments demonstrating that GB004 treatment protected epithelial cells from TNFa-induced cell apoptosis, improving both epithelial cell number and tight junction protein ZO-1 staining. Conclusion GB004 modulates key anti-inflammatory and immunomodulatory activities in human co-culture systems. Furthermore, GB004 demonstrates protective effects on human derived monolayer cultures by reducing cell death, promoting tight junction formation, and improving barrier integrity. Targeting both barrier function and local colonic inflammation represents a multi-faceted approach to treatment of inflammatory bowel disease. A phase 2 clinical study of GB004 is ongoing in patients with ulcerative colitis (NCT04556383). Sponsored by GB004, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

scholarly journals KIBRA-aPKC Connection: High expression of KIBRA in High Invasion and Poor Prognosis. Overexpression of the aPKC-binding region of KIBRA affects tight junction formation in epithelial cells.

2013 ◽  
Vol 104 (2) ◽  
pp. February cover-February cover ◽  
Author(s):  
Yohei Yoshihama ◽  
Yusuke Izumisawa ◽  
Kazunori Akimoto ◽  
Yoshinori Satoh ◽  
Taichi Mizushima ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Poor Prognosis ◽  
High Expression ◽  
Binding Region ◽  
Tight Junction Formation ◽  
Junction Formation

LSR defines cell corners for tricellular tight junction formation in epithelial cells

2011 ◽  
Vol 124 (4) ◽  
pp. 548-555 ◽  
Author(s):  
S. Masuda ◽  
Y. Oda ◽  
H. Sasaki ◽  
J. Ikenouchi ◽  
T. Higashi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junction Formation ◽  
Junction Formation

scholarly journals Nonreceptor Tyrosine Kinase c-Yes Interacts with Occludin during Tight Junction Formation in Canine Kidney Epithelial Cells

2002 ◽  
Vol 13 (4) ◽  
pp. 1227-1237 ◽  
Author(s):  
Yan-Hua Chen ◽  
Qun Lu ◽  
Daniel A. Goodenough ◽  
Beverly Jeansonne
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Tight Junction ◽  
Tyrosine Phosphorylation ◽  
Nonreceptor Tyrosine Kinase ◽  
Tight Junction Formation ◽  
Kinase C ◽  
Junction Formation ◽  
Kidney Epithelial Cells ◽  
Canine Kidney

Occludin is an integral membrane protein that is tyrosine phosphorylated when localized at tight junctions. When Ca2+was depleted from the culture medium, occludin tyrosine phosphorylation was diminished from Madin-Darby canine kidney epithelial cells in 2 min. This dephosphorylation was correlated with a significant reduction in transepithelial electrical resistance (TER), indicating a global loss of the tight junction barrier function. Reconstitution of Ca2+ resulted in a robust tyrosine rephosphorylation of occludin that was temporally associated with an increase in TER. Moreover, we demonstrate in this study that occludin was colocalized with the nonreceptor tyrosine kinase c-Yes at cell junction areas and formed an immunoprecipitable complex with c-Yes in vivo. This complex dissociated when the cells were incubated in medium without Ca2+ or treated with a c-Yes inhibitor, CGP77675. In the presence of CGP77675 after Ca2+ repletion, occludin tyrosine phosphorylation was completely abolished and both tight junction formation and the increase of the TER were inhibited. Our study thus provides strong evidence that occludin tyrosine phosphorylation is tightly linked to tight junction formation in epithelial cells, and that the nonreceptor tyrosine kinase c-Yes is involved in the regulation of this process.

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