scholarly journals Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation

Biology Open ◽  
2012 ◽  
Vol 1 (11) ◽  
pp. 1128-1140 ◽  
Author(s):  
F. Twiss ◽  
Q. Le Duc ◽  
S. Van Der Horst ◽  
H. Tabdili ◽  
G. Van Der Krogt ◽  
...  
2019 ◽  
Author(s):  
Bethany M. Young ◽  
Keerthana Shankar ◽  
Cindy K. Tho ◽  
Amanda R. Pellegrino ◽  
Rebecca L. Heise

ABSTRACTDecellularized tissues offer a unique tool for developing regenerative biomaterials orin vitroplatforms for the study of cell-extracellular matrix (ECM) interactions. One main challenge associated with decellularized lung tissue is that ECM components can be stripped away or altered by the detergents used to remove cellular debris. Without characterizing the composition of lung decellularized ECM (dECM) and the cellular response caused by the altered composition, it is difficult to utilize dECM for regeneration and specifically, engineering the complexities of the alveolar-capillary barrier. This study takes steps towards uncovering if dECM must be enhanced with lost ECM proteins to achieve proper epithelial barrier formation. To achieve this, epithelial barrier function was assessed on dECM coatings with and without the systematic addition of several key basement membrane proteins. After comparing barrier function on collagen, fibronectin, laminin, and dECM in varying combinations as anin vitrocoating, the alveolar epithelium exhibited superior barrier function when dECM was supplemented with laminin as evidenced by trans-epithelial electrical resistance (TEER) and permeability assays. Increased barrier resistance with laminin addition was associated with upregulation of Claudin-18, E- cadherin, and junction adhesion molecule (JAM)-A, and stabilization of zonula occludens (ZO)-1 at junction complexes. The Epac/Rap1 pathway was observed to play a role in the ECM-mediated barrier function determined by protein expression and Epac inhibition. These findings reveal potential ECM coatings and molecular therapeutic targets for improved regeneration with decellularized scaffolds or edema related pathologies.


Thorax ◽  
1997 ◽  
Vol 52 (3) ◽  
pp. 213-217 ◽  
Author(s):  
J. S. Erjefalt ◽  
F. Sundler ◽  
C. G. Persson

2020 ◽  
Vol 21 (14) ◽  
pp. 5067
Author(s):  
Alexander G. Markov ◽  
Arina A. Fedorova ◽  
Violetta V. Kravtsova ◽  
Anastasia E. Bikmurzina ◽  
Larisa S. Okorokova ◽  
...  

The ability of exogenous low ouabain concentrations to affect claudin expression and therefore epithelial barrier properties was demonstrated previously in cultured cell studies. We hypothesized that chronic elevation of circulating ouabain in vivo can affect the expression of claudins and tight junction permeability in different tissues. We tested this hypothesis in rats intraperitoneally injected with ouabain (1 μg/kg) for 4 days. Rat jejunum, colon and brain frontal lobes, which are variable in the expressed claudins and tight junction permeability, were examined. Moreover, the porcine jejunum cell line IPEC-J2 was studied. In IPEC-J2-cells, ouabain (10 nM, 19 days of incubation) stimulated epithelial barrier formation, increased transepithelial resistance and the level of cSrc-kinase activation by phosphorylation, accompanied with an increased expression of claudin-1, -5 and down-regulation of claudin-12; the expression of claudin-3, -4, -8 and tricellulin was not changed. In the jejunum, chronic ouabain increased the expression of claudin-1, -3 and -5 without an effect on claudin-2 and -4 expression. In the colon, only down-regulation of claudin-3 was observed. Chronic ouabain protected the intestine transepithelial resistance against functional injury induced by lipopolysaccharide treatment or by modeled acute microgravity; this regulation was most pronounced in the jejunum. Claudin-1 was also up-regulated in cerebral blood vessels. This was associated with reduction of claudin-3 expression while the expression of claudin-5 and occludin was not affected. Altogether, our results confirm that circulating ouabain can functionally and tissue-specifically affect barrier properties of epithelial and endothelial tissues via Na,K-ATPase-mediated modulation of claudins expression.


BioEssays ◽  
2005 ◽  
Vol 27 (10) ◽  
pp. 987-990 ◽  
Author(s):  
Bernard Moussian ◽  
Anne E. Uv

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Shere Paris ◽  
Daniel Davis ◽  
Eitan Podgaetz ◽  
Steven Leeds ◽  
Marc Ward ◽  
...  

2019 ◽  
Vol 218 (10) ◽  
pp. 3372-3396 ◽  
Author(s):  
Tetsuhisa Otani ◽  
Thanh Phuong Nguyen ◽  
Shinsaku Tokuda ◽  
Kei Sugihara ◽  
Taichi Sugawara ◽  
...  

Tight junctions (TJs) establish the epithelial barrier and are thought to form a membrane fence to regulate epithelial polarity, although the roles of TJs in epithelial polarity remain controversial. Claudins constitute TJ strands in conjunction with the cytoplasmic scaffolds ZO-1 and ZO-2 and play pivotal roles in epithelial barrier formation. However, how claudins and other TJ membrane proteins cooperate to organize TJs remains unclear. Here, we systematically knocked out TJ components by genome editing and show that while ZO-1/ZO-2–deficient cells lacked TJ structures and epithelial barriers, claudin-deficient cells lacked TJ strands and an electrolyte permeability barrier but formed membrane appositions and a macromolecule permeability barrier. Moreover, epithelial polarity was disorganized in ZO-1/ZO-2–deficient cells, but not in claudin-deficient cells. Simultaneous deletion of claudins and a TJ membrane protein JAM-A resulted in a loss of membrane appositions and a macromolecule permeability barrier and in sporadic epithelial polarity defects. These results demonstrate that claudins and JAM-A coordinately regulate TJ formation and epithelial polarity.


2019 ◽  
Vol 55 (3) ◽  
pp. 252-254 ◽  
Author(s):  
A. A. Fedorova ◽  
V. Cornelius ◽  
S. Amasheh ◽  
I. I. Krivoi ◽  
A. G. Markov

2021 ◽  
Vol 7 (47) ◽  
Author(s):  
Yukako Oda ◽  
Chisato Takahashi ◽  
Shota Harada ◽  
Shun Nakamura ◽  
Daxiao Sun ◽  
...  

2009 ◽  
Vol 83 (12) ◽  
pp. 6125-6134 ◽  
Author(s):  
Guruprasad R. Medigeshi ◽  
Alec J. Hirsch ◽  
James D. Brien ◽  
Jennifer L. Uhrlaub ◽  
Peter W. Mason ◽  
...  

ABSTRACT During acute infection, West Nile virus (WNV) has been reported to infect a variety of cell types in various tissues of both experimentally and naturally infected hosts. Virus infects epithelial cells in the skin, kidney, intestine, and testes, although the importance of these findings is unclear. In the current study, we have observed that WNV infection of kidney tubules in mice coincides with the loss of expression of several members of the claudin family. Proteins of this family are often involved in epithelial barrier formation and function. WNV infection of epithelial cells in culture resulted in a decrease in the transepithelial electrical resistance, an increase in the efflux of mannitol across the monolayer, and a loss of intracellular levels of claudin-1 to -4. WNV capsid alone was sufficient for the degradation event, which was mediated through lysosomal proteases. Since epithelial cells are frequent sites of WNV infection, these observations imply a potential mechanism for virus dissemination and extraneural pathogenesis.


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