Role of VASP in reestablishment of epithelial tight  junction assembly after Ca<sup>2+</sup> switch

Lawrence, Donald W.; Comerford, Katrina M.; Colgan, Sean P.

doi:10.1152/ajpcell.00288.2001

Cited by 88 publications

(102 citation statements)

References 63 publications

(50 reference statements)

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“…Adenosine produced in this manner is then available to bind apically expressed adenosine receptors on the epithelium, a binding interaction that has been implicated in the reestablishment of epithelial tight junction complexes and epithelial barrier function. 61,62 These findings are consistent with tightly regulated signaling events that allow neutrophils to squeeze between epithelial cells without causing a significant leak. Unfortunately, few if any studies have modeled low levels of neutrophil transepithelial migration.…”

Section: Neutrophil-epithelial Interactionssupporting

confidence: 56%

Neutrophil-Epithelial Interactions

Parkos

2016

The American Journal of Pathology

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Section: Neutrophil-epithelial Interactionssupporting

confidence: 56%

Neutrophil-Epithelial Interactions

Parkos

2016

The American Journal of Pathology

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“…PLY instillation (6.125 μg/kg) in male C57BL6 mice (n = 5 per group; mean ± SD; *P < 0.03 vs. control; # P < 0.02 vs. PLY). (32,33). Moreover, PKA activation in endothelial cells can result in inhibition of Rho kinase by direct phosphorylation of Rho GDPdissociation inhibitor (RhoGDI), thus preventing the release of the barrier-disruptive RhoA from the RhoA-RhoGDI complex (34).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, PKA activation in endothelial cells can result in inhibition of Rho kinase by direct phosphorylation of Rho GDPdissociation inhibitor (RhoGDI), thus preventing the release of the barrier-disruptive RhoA from the RhoA-RhoGDI complex (34). Besides, cAMP potentiates VE-cadherin-mediated cell-cell contacts, thus enhancing endothelial barrier function (32,33). Phosphorylation of VE-cadherin at Tyr 658 leads to dissociation of this major AJ protein from p120-catenin, which serves as a factor that stabilizes AJ and prevents VE-cadherin endocytosis (28,29).…”

Section: Discussionmentioning

confidence: 99%

Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema

Lucas

Sridhar

Rick

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Aggressive treatment with antibiotics in patients infected with Streptococcus pneumoniae induces release of the bacterial virulence factor pneumolysin (PLY). Days after lungs are sterile, this pore-forming toxin can still induce pulmonary permeability edema in patients, characterized by alveolar/capillary barrier dysfunction and impaired alveolar liquid clearance (ALC). ALC is mainly regulated through Na + transport by the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed Na + /K + -ATPase in type II alveolar epithelial cells. Because no standard treatment is currently available to treat permeability edema, the search for novel therapeutic candidates is of high priority. We detected mRNA expression for the active receptor splice variant SV1 of the hypothalamic polypeptide growth hormone-releasing hormone (GHRH), as well as for GHRH itself, in human lung microvascular endothelial cells (HL-MVEC). Therefore, we have evaluated the effect of the GHRH agonist JI-34 on PLY-induced barrier and ALC dysfunction. JI-34 blunts PLY-mediated endothelial hyperpermeability in monolayers of HL-MVEC, in a cAMP-dependent manner, by means of reducing the phosphorylation of myosin light chain and vascular endothelial (VE)-cadherin. In human airway epithelial H441 cells, PLY significantly impairs Na + uptake, but JI-34 restores it to basal levels by means of increasing cAMP levels. Intratracheal instillation of PLY into C57BL6 mice causes pulmonary alveolar epithelial and endothelial hyperpermeability as well as edema formation, all of which are blunted by JI-34. These findings point toward a protective role of the GHRH signaling pathway in PLY-induced permeability edema.pneumonia | cyclic AMP

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“…There was no significant effect on cGMP, again consistent with the enhanced activity of stimulated PDE2A toward cAMP. cAMP is a key defensive signaling molecule in the injured lung, opposing LPS-and ROS-mediated cell death, preserving endothelial and epithelial intercellular junctions, and enhancing edema clearance (16,21,23,26,28,38). For example, increased PDE2A expression in human umbilical vein endothelium was recently reported to increase thrombin-induced NADPH oxidase activity and ROS production by a loss of cAMP inhibition of rac1 activity (14).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury

Rentsendorj

Damarla

Aggarwal

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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is stimulated by cGMP to hydrolyze cAMP, a potent endothelial barrier-protective molecule. We previously found that lung PDE2A contributed to a mouse model of ventilator-induced lung injury (VILI). The purpose of the present study was to determine the contribution of PDE2A in a two-hit mouse model of 1-day intratracheal (IT) LPS followed by 4 h of 20 ml/kg tidal volume ventilation. Compared with IT water controls, LPS alone (3.75 g/g body wt) increased lung PDE2A mRNA and protein expression by 6 h with a persistent increase in protein through day 4 before decreasing to control levels on days 6 and 10. Similar to the PDE2A time course, the peak in bronchoalveolar lavage (BAL) neutrophils, lactate dehydrogenase (LDH), and protein concentration also occurred on day 4 post-LPS. IT LPS (1 day) and VILI caused a threefold increase in lung PDE2A and inducible nitric oxide synthase (iNOS) and a 24-fold increase in BAL neutrophilia. Compared with a control adenovirus, PDE2A knockdown with an adenovirus expressing a short hairpin RNA administered IT 3 days before LPS/VILI effectively decreased lung PDE2A expression and significantly attenuated BAL neutrophilia, LDH, protein, and chemokine levels. PDE2A knockdown also reduced lung iNOS expression by 53%, increased lung cAMP by nearly twofold, and improved survival from 47 to 100%. We conclude that in a mouse model of LPS/VILI, a synergistic increase in lung PDE2A expression increased lung iNOS and alveolar inflammation and contributed significantly to the ensuing acute lung injury.lipopolysaccharide; ventilator-induced; cyclic guanosine monophosphate; inducible nitric oxide synthase; cAMP SEVERE PNEUMONIA IS A FREQUENT cause of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) (49). ARDS is characterized by neutrophil infiltration, the generation of toxic cytokines and reactive oxygen species (ROS), increased NO production and the loss of endothelial and epithelial barrier function (4). These features can be reproduced in animal models by the installation of intratracheal (IT) LPS (10, 24, 31), a key component of the gram-negative bacterial cell wall. LPS, through Toll-like receptor-4 signaling, was shown to cause increased NO from phosphorylated endothelial (eNOS) (11) and inducible nitric oxide synthase (iNOS) (24, 31) in alveolar macrophages, neutrophils, epithelium, and endothelium. NO from both eNOS and iNOS was found to play a major pathogenic role in ALI from LPS (24, 31, 42) and in ventilator-induced lung injury (VILI) (33, 39). These injurious effects of endogenous NO have been attributed to a reaction with superoxide to generate peroxynitrite (31, 33). In both LPS-induced ALI (47) and VILI (39), however, NO also activates soluble guanylyl cyclase (sGC), increasing production of cGMP in multiple cell types including endothelium (39), epithelium (9, 17), and macrophages (3).The effects of cGMP signaling in ALI are complex, depending on cell type, intracellular compartmentalization, and the downstream cGMP targets (39). These targets include...

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Role of VASP in reestablishment of epithelial tight junction assembly after Ca²⁺ switch

Cited by 88 publications

References 63 publications

Neutrophil-Epithelial Interactions

Neutrophil-Epithelial Interactions

Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury

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Role of VASP in reestablishment of epithelial tight junction assembly after Ca2+ switch

Cited by 88 publications

References 63 publications

Neutrophil-Epithelial Interactions

Neutrophil-Epithelial Interactions

Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury

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Role of VASP in reestablishment of epithelial tight junction assembly after Ca²⁺ switch