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Long-term cyclic stretch controls pulmonary endothelial permeability at translational and post-translational levels.
- Source :
-
Experimental cell research [Exp Cell Res] 2008 Nov 15; Vol. 314 (19), pp. 3466-77. Date of Electronic Publication: 2008 Sep 19. - Publication Year :
- 2008
-
Abstract
- We have previously described differential effects of physiologic (5%) and pathologic (18%) cyclic stretch (CS) on agonist-induced pulmonary endothelial permeability. This study examined acute and chronic effects of CS on agonist-induced intracellular signaling and cell morphology in the human lung macro- and microvascular endothelial cell (EC) monolayers. Endothelial permeability was assessed by analysis of morphological changes, parameters of cell contraction and measurements of transendothelial electrical resistance. Exposure of both microvascular and macrovascular EC to 18% CS for 2-96 h increased thrombin-induced permeability and monolayer disruption. Interestingly, the ability to promote thrombin responses was present in EC cultures exposed to 48-96 h of CS even after replating onto non-elastic substrates. In turn, physiologic CS preconditioning (72 h) attenuated thrombin-induced paracellular gap formation and MLC phosphorylation in replated EC cultures. Long-term preconditioning at 18% CS (72 h) increased the content of signaling and contractile proteins including Rho GTPase, MLC, MLC kinase, ZIP kinase, PAR1, caldesmon and HSP27 in the pulmonary microvascular and macrovascular cells. We conclude that short term CS regulates EC permeability via modulation of agonist-induced signaling, whereas long-term CS controls endothelial barrier at both post-translational level and via magnitude-dependent regulation of pulmonary EC phenotype, signaling and contractile protein expression.
- Subjects :
- Cells, Cultured
Humans
Intracellular Signaling Peptides and Proteins metabolism
Permeability
Reactive Oxygen Species metabolism
Signal Transduction
Stress, Mechanical
Thrombin metabolism
Thrombin pharmacology
Capillary Permeability physiology
Endothelial Cells metabolism
Lung cytology
Lung metabolism
Protein Modification, Translational physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 314
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 18824167
- Full Text :
- https://doi.org/10.1016/j.yexcr.2008.09.003