Anthrax Edema Toxin Co-Opts IGF1R and EGFR Signaling to Promote Cell-Cell Barrier Dysfunction

2019 ◽  
Author(s):  
Prashant Jain ◽  
Mahtab Moayeri ◽  
Annabel Guichard ◽  
Stephen Leppla ◽  
Ethan Bier
Keyword(s):  
Egfr Signaling ◽  
Barrier Dysfunction ◽  
Edema Toxin ◽  
Cell Cell

scholarly journals ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes

2013 ◽  
Vol 33 (16) ◽  
pp. 3077-3090 ◽  
Author(s):  
Katherine C. Hall ◽  
Daniel Hill ◽  
Miguel Otero ◽  
Darren A. Plumb ◽  
Dara Froemel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Terminal Differentiation ◽  
Cell Interactions ◽  
Hypertrophic Chondrocytes ◽  
Main Role ◽  
Egfr Signaling ◽  
Cell Cell

Endochondral ossification is a highly regulated process that relies on properly orchestrated cell-cell interactions in the developing growth plate. This study is focused on understanding the role of a crucial regulator of cell-cell interactions, the membrane-anchored metalloproteinase ADAM17, in endochondral ossification. ADAM17 releases growth factors, cytokines, and other membrane proteins from cells and is essential for epidermal growth factor receptor (EGFR) signaling and for processing tumor necrosis factor alpha. Here, we report that mice lacking ADAM17 in chondrocytes (A17ΔCh) have a significantly expanded zone of hypertrophic chondrocytes in the growth plate and retarded growth of long bones. This abnormality is caused by an accumulation of the most terminally differentiated type of chondrocytes that produces a calcified matrix. Inactivation of ADAM17 in osteoclasts or endothelial cells does not affect the zone of hypertrophic chondrocytes, suggesting that the main role of ADAM17 in the growth plate is in chondrocytes. This notion is further supported byin vitroexperiments showing enhanced hypertrophic differentiation of primary chondrocytes lackingAdam17. The enlarged zone of hypertrophic chondrocytes inA17ΔChmice resembles that described in mice with mutant EGFR signaling or lack of its ligand transforming growth factor α (TGFα), suggesting that ADAM17 regulates terminal differentiation of chondrocytes during endochondral ossification by activating the TGFα/EGFR signaling axis.

scholarly journals Pulmonary epithelial barrier function: some new players and mechanisms

2015 ◽  
Vol 308 (8) ◽  
pp. L731-L745 ◽  
Author(s):  
Kieran Brune ◽  
James Frank ◽  
Andreas Schwingshackl ◽  
James Finigan ◽  
Venkataramana K. Sidhaye
Keyword(s):  
Lung Injury ◽  
Ion Transport ◽  
Ion Homeostasis ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Pulmonary Epithelium ◽  
Structural Element ◽  
Barrier Regulation ◽  
Cell Cell

The pulmonary epithelium serves as a barrier to prevent access of the inspired luminal contents to the subepithelium. In addition, the epithelium dictates the initial responses of the lung to both infectious and noninfectious stimuli. One mechanism by which the epithelium does this is by coordinating transport of diffusible molecules across the epithelial barrier, both through the cell and between cells. In this review, we will discuss a few emerging paradigms of permeability changes through altered ion transport and paracellular regulation by which the epithelium gates its response to potentially detrimental luminal stimuli. This review is a summary of talks presented during a symposium in Experimental Biology geared toward novel and less recognized methods of epithelial barrier regulation. First, we will discuss mechanisms of dynamic regulation of cell-cell contacts in the context of repetitive exposure to inhaled infectious and noninfectious insults. In the second section, we will briefly discuss mechanisms of transcellular ion homeostasis specifically focused on the role of claudins and paracellular ion-channel regulation in chronic barrier dysfunction. In the next section, we will address transcellular ion transport and highlight the role of Trek-1 in epithelial responses to lung injury. In the final section, we will outline the role of epithelial growth receptor in barrier regulation in baseline, acute lung injury, and airway disease. We will then end with a summary of mechanisms of epithelial control as well as discuss emerging paradigms of the epithelium role in shifting between a structural element that maintains tight cell-cell adhesion to a cell that initiates and participates in immune responses.

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.

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.

Application of Spurr, LX112, LX112/ARALDITE 502, POLY/BED 812 and Effapoxy Embedding Media to in Vitro Agar-Cultured Bone Marrow Colonies.

1980 ◽  
Vol 38 ◽  
pp. 646-647
Author(s):  
Glenn M. Buchanan ◽  
Dennis A. Stewart
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Cell Cell

In vitro bone-marrow derived colonies cultured in agar and prepared in Epon 812 for electron microscopy occassionally produce blocks that are too soft for sectioning. We attribute this softness to the retention, after standard dehydration, of water by the agar and to the relatively slow penetration of the agar by Epon-based embedding media. The agar cannot be removed or replaced since this would disrupt the colony integrity and prevent the study of cell-cell relationships. This paper describes the procedures and results of more extensive specimen dehydration and of embedding with Epon-replacement formulations.

622: Von Hippel-Lindau Inactivation Downregulates the Cell-Cell Adhesion Molecule E Cadherin in Renal Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 170-170
Author(s):  
Maxine G. Tran ◽  
Miguel A. Esteban ◽  
Peter D. Hill ◽  
Ashish Chandra ◽  
Tim S. O'Brien ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Von Hippel Lindau ◽  
E Cadherin ◽  
Cell Cell
Sign in / Sign up

Export Citation Format

Share Document