scholarly journals The mechanism of serine protease‐induced increases in epithelial barrier function in intestinal epithelial cells (60.7)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Kelcie Lahey ◽  
Wallace MacNaughton
Keyword(s):  
Epithelial Cells ◽  
Serine Protease ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Barrier Function

scholarly journals JunD Represses Transcription and Translation of the Tight Junction Protein Zona Occludens-1 Modulating Intestinal Epithelial Barrier Function

2008 ◽  
Vol 19 (9) ◽  
pp. 3701-3712 ◽  
Author(s):  
Jie Chen ◽  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Mrna Translation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO-1 mRNA translation by enhancing the interaction of the ZO-1 3′-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.

Polyamines are necessary for synthesis and stability of occludin protein in intestinal epithelial cells

2005 ◽  
Vol 288 (6) ◽  
pp. G1159-G1169 ◽  
Author(s):  
Xin Guo ◽  
Jaladanki N. Rao ◽  
Lan Liu ◽  
Tongtong Zou ◽  
Kaspar M. Keledjian ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Integral Membrane Protein ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

Occludin is an integral membrane protein that forms the sealing element of tight junctions and is critical for epithelial barrier function. Polyamines are implicated in multiple signaling pathways driving different biological functions of intestinal epithelial cells (IEC). The present study determined whether polyamines are involved in expression of occludin and play a role in intestinal epithelial barrier function. Studies were conducted in stable Cdx2-transfected IEC-6 cells (IEC-Cdx2L1) associated with a highly differentiated phenotype. Polyamine depletion by α-difluoromethylornithine (DFMO) decreased levels of occludin protein but failed to affect expression of its mRNA. Other tight junction proteins, zonula occludens (ZO)-1, ZO-2, claudin-2, and claudin-3, were also decreased in polyamine-deficient cells. Decreased levels of tight junction proteins in DFMO-treated cells were associated with dysfunction of the epithelial barrier, which was overcome by exogenous polyamine spermidine. Decreased levels of occludin in polyamine-deficient cells was not due to the reduction of intracellular-free Ca2+ concentration ([Ca2+]cyt), because either increased or decreased [Ca2+]cyt did not alter levels of occludin in the presence or absence of polyamines. The level of newly synthesized occludin protein was decreased by ∼70% following polyamine depletion, whereas its protein half-life was reduced from ∼120 min in control cells to ∼75 min in polyamine-deficient cells. These findings indicate that polyamines are necessary for the synthesis and stability of occludin protein and that polyamine depletion disrupts the epithelial barrier function, at least partially, by decreasing occludin.

scholarly journals The HIF target ATG9A is essential for epithelial barrier function and tight junction biogenesis

2020 ◽  
Vol 31 (20) ◽  
pp. 2249-2258
Author(s):  
Alexander S. Dowdell ◽  
Ian M. Cartwright ◽  
Matthew S. Goldberg ◽  
Rachael Kostelecky ◽  
Tyler Ross ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Hypoxia Inducible Factor ◽  
Epithelial Barrier ◽  
Adaptation To Hypoxia ◽  
Intestinal Epithelial ◽  
Hypoxia Response ◽  
Epithelial Barrier Function

The transcription factor hypoxia-inducible factor (HIF) mediates adaptation to hypoxia. We found that HIF regulates the autophagy protein ATG9A in intestinal epithelial cells. Subsequent knockdown of ATG9A resulted in tight junction mislocalization and cytoskeletal defects. These results suggest a link among the hypoxia response, autophagy, and junctional biogenesis.

scholarly journals Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5597 ◽  
Author(s):  
Deborah Delbue ◽  
Danielle Cardoso-Silva ◽  
Federica Branchi ◽  
Alice Itzlinger ◽  
Marilena Letizia ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Surface Marker ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Surface Marker Expression ◽  
Barrier Defect ◽  
Marker Expression

Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from active and inactive CeD patients and healthy controls. PBMCs were sorted for expression of CD14 and co-cultured with intestinal epithelial cells (IECs, Caco2BBe). Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. Transepithelial resistance was found to be decreased only in IECs that had been exposed to celiac monocytes. In line with this, tight junctional alterations were found by confocal laser scanning microscopy and Western blotting of ZO-1, occludin, and claudin-5. Analysis of cytokine concentrations in monocyte supernatants revealed higher expression of interleukin-6 and MCP-1 in celiac monocytes. However, surface marker expression, as analyzed by FACS analysis after immunostaining, did not reveal significant alterations in celiac monocytes. In conclusion, CeD peripheral monocytes reveal an intrinsically elevated pro-inflammatory cytokine pattern that is associated with the potential of peripheral monocytes to affect barrier function by altering TJ composition.

The enteric nervous system as a regulator of intestinal epithelial barrier function in health and disease

2010 ◽  
Vol 4 (5) ◽  
pp. 637-651 ◽  
Author(s):  
Susanne A Snoek ◽  
Marleen I Verstege ◽  
Guy E Boeckxstaens ◽  
René M van den Wijngaard ◽  
Wouter J de Jonge
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Health And Disease

scholarly journals Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature

2013 ◽  
Vol 33 (10) ◽  
pp. 1457-1469 ◽  
Author(s):  
Kirsten E. Pijls ◽  
Daisy M. A. E. Jonkers ◽  
Elhaseen E. Elamin ◽  
Ad A. M. Masclee ◽  
Ger H. Koek
Keyword(s):  
Liver Cirrhosis ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Extensive Review ◽  
Review Of The Literature ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function
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