Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling

2014 ◽  
Vol 306 (12) ◽  
pp. C1154-C1166 ◽  
Author(s):  
Najmunnisa Nasreen ◽  
Nazli Khodayari ◽  
Peruvemba S. Sriram ◽  
Jawaharlal Patel ◽  
Kamal A. Mohammed
Keyword(s):  
Focal Adhesion ◽  
Tobacco Smoke ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Eph Receptors ◽  
Barrier Dysfunction ◽  
Developmental Processes ◽  
Epithelial Barrier Dysfunction ◽  
E Cadherin ◽  
Cell Cell

Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that mediate various cellular and developmental processes. The degrees of expression of these key molecules control the cell-cell interactions. Although the role of Eph receptors and their ligand Ephrins is well studied in developmental processes, their function in tobacco smoke (TS)-induced epithelial barrier dysfunction is unknown. We hypothesized that TS may induce permeability in bronchial airway epithelial cell (BAEpC) monolayer by modulating receptor EphA2 expression, actin cytoskeleton, adherens junction, and focal adhesion proteins. Here we report that in BAEpCs, acute TS exposure significantly upregulated EphA2 and EphrinA1 expression, disrupted the actin filaments, decreased E-cadherin expression, and increased protein permeability, whereas the focal adhesion protein paxillin was unaffected. Silencing the receptor EphA2 expression with silencing interference RNA (siRNA) significantly attenuated TS-induced hyperpermeability in BAEpCs. In addition, when BAEpC monolayer was transfected with EphA2-expressing plasmid and treated with recombinant EphrinA1, the transepithelial electrical resistance decreased significantly. Furthermore, TS downregulated E-cadherin expression and induced hyperpermeability across BAEpC monolayer in a Erk1/Erk2, p38, and JNK MAPK-dependent manner. TS induced hyperpermeability in BAEpC monolayer by targeting cell-cell adhesions, and interestingly cell-matrix adhesions were unaffected. The present data suggest that TS causes significant damage to the BAEpCs via induction of EphA2 and downregulation of E-cadherin. Induction of EphA2 in the BAEpCs exposed to TS may be an important signaling event in the pathogenesis of TS-induced epithelial injury.

scholarly journals CUGBP1 and HuR regulate E-cadherin translation by altering recruitment of E-cadherin mRNA to processing bodies and modulate epithelial barrier function

2016 ◽  
Vol 310 (1) ◽  
pp. C54-C65 ◽  
Author(s):  
Ting-Xi Yu ◽  
Bei-Lin Gu ◽  
Jun-Kai Yan ◽  
Jie Zhu ◽  
Wei-Hui Yan ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intestinal Barrier ◽  
Primary Component ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Processing Bodies ◽  
Epithelial Barrier Function ◽  
Epithelial Barrier Dysfunction ◽  
E Cadherin

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3′-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions.

Role of focal adhesion kinase in burn induced gut epithelial barrier dysfunction

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Fang Wang ◽  
Rebecca A. Eitnier ◽  
Alexandra M. Aponte ◽  
Thomas J. Ewing ◽  
Mack H. Wu
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Dysfunction

scholarly journals Lipopolysaccharide-induced phosphorylation of c-Met tyrosine residue 1003 regulates c-Met intracellular trafficking and lung epithelial barrier function

2013 ◽  
Vol 305 (1) ◽  
pp. L56-L63 ◽  
Author(s):  
Yutong Zhao ◽  
Jing Zhao ◽  
Rachel K. Mialki ◽  
Jianxin Wei ◽  
Ernst W. Spannhake ◽  
...  
Keyword(s):  
Serine Phosphorylation ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Tyrosine Residue ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Barrier Integrity ◽  
Cell Contacts ◽  
Lung Epithelial ◽  
Cell Cell

c-Met, the receptor tyrosine kinase whose natural ligand is hepatocyte growth factor, is known to have a key role in cell motility. We have previously shown that lysophosphatidic acid (LPA) induced a decrease in c-Met activation via serine phosphorylation of c-Met at cell-cell contacts. Here, we demonstrate that lipopolysaccharide (LPS) treatment of human bronchial epithelial cells induced internalization of c-Met via phosphorylation at its tyrosine residue 1003. In addition, it induced epithelial barrier dysfunction as evidenced by a decrease in transepithelial resistance (TER) in a time-dependent manner. Pretreatment with a c-Met inhibitor (PHA-665752) or inhibition of protein kinase C (PKC)-α attenuated the LPS-mediated phosphorylation of c-Met and its internalization. LPS-induced c-Met tyrosine 1003 phosphorylation, activation of PKCα, and c-Met internalization were, however, reversed by pretreatment of cells with LPA, which increased c-Met accumulation at cell-cell contacts. Inhibition of LPS-mediated c-Met tyrosine (Y1003) phosphorylation and internalization by prior treatment with PHA-665752, inhibition of PKCα, or overexpression of c-MetY1003A mutant attenuated LPS-induced reduction of TER. Furthermore, we found that c-Met accumulation at cell-cell contacts contributed to LPA-enhanced epithelial barrier integrity, since downregulation of c-Met by specific small-interfering RNA attenuated LPA-increased TER. The data reveal a novel biological function of c-Met in the regulation of lung epithelial barrier integrity.

NAD+ Ameliorates Inflammation-Induced Epithelial Barrier Dysfunction in Cultured Enterocytes and Mouse Ileal Mucosa

2003 ◽  
Vol 307 (2) ◽  
pp. 443-449 ◽  
Author(s):  
Xiaonan Han ◽  
Takashi Uchiyama ◽  
Penny L. Sappington ◽  
Arino Yaguchi ◽  
Runkuan Yang ◽  
...  
Keyword(s):  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Ileal Mucosa ◽  
Epithelial Barrier Dysfunction

scholarly journals Intestinal Epithelial Barrier Dysfunction in Food Hypersensitivity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Linda Chia-Hui Yu
Keyword(s):  
Mast Cell ◽  
Cell Surface ◽  
Critical Role ◽  
Mast Cell Activation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Food Antigens ◽  
Epithelial Barrier Dysfunction

Intestinal epithelial barrier plays a critical role in the maintenance of gut homeostasis by limiting the penetration of luminal bacteria and dietary allergens, yet allowing antigen sampling for the generation of tolerance. Undigested proteins normally do not gain access to the lamina propria due to physical exclusion by tight junctions at the cell-cell contact sites and intracellular degradation by lysosomal enzymes in enterocytes. An intriguing question then arises: how do macromolecular food antigens cross the epithelial barrier? This review discusses the epithelial barrier dysfunction in sensitized intestine with special emphasis on the molecular mechanism of the enhanced transcytotic rates of allergens. The sensitization phase of allergy is characterized by antigen-induced cross-linking of IgE bound to high affinity FcεRI on mast cell surface, leading to anaphylactic responses. Recent studies have demonstrated that prior to mast cell activation, food allergens are transported in large quantity across the epithelium and are protected from lysosomal degradation by binding to cell surface IgE and low-affinity receptor CD23/FcεRII. Improved immunotherapies are currently under study including anti-IgE and anti-CD23 antibodies for the management of atopic disorders.

Correlation between cyclical epithelial barrier dysfunction and bacterial translocation in the relapses of intestinal inflammation

2006 ◽  
Vol 12 (9) ◽  
pp. 843-852 ◽  
Author(s):  
Monica Porras ◽  
Maria Teresa Martín ◽  
Ping-Chang Yang ◽  
Jennifer Jury ◽  
Mary H. Perdue ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Intestinal Inflammation ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Dysfunction
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