| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;
* Tufts University/New England Medical Center, Boston, Massachusetts, USA; and
National Cancer Institute, Bethesda, Maryland, USA
The stabilization of endothelial cell (EC) barrier function within newly formed capillaries is a critical feature of angiogenesis. We examined human lung EC barrier regulation elicited by hepatocyte growth factor (HGF), a recognized angiogenic factor and EC chemoattractant. HGF rapidly and dose-dependently elevated transendothelial electrical resistance (TER) of EC monolayers (>50% increase at 100 ng/ml), with immunofluorescence microscopic evidence of both cytoplasmic actin stress fiber dissolution and strong augmentation of the cortical actin ring. HGF rapidly stimulated phosphatidylinositol 3'-kinase, ERK, p38 mitogen-activated protein kinase, and protein kinase C activities. Pharmacological inhibitor studies demonstrated each pathway to be intimately involved in HGF-induced increases in TER, cortical actin thickening, and phosphorylation of the Ser/Thr glycogen synthase kinase-3ß (GSK-3ß), a potential target for the HGF barrier-promoting response. GSK-3ß phosphorylation was strongly correlated with reductions in both HGF-induced TER and enhanced ß-catenin immunoreactivity observed at cell-cell junctions. Our data suggest a model in which HGF-mediated EC cytoskeletal rearrangement and barrier enhancement depend critically on the activation of a complex kinase cascade that converges at GSK-3ß to increase the availability of ß-catenin, thereby enhancing endothelial junctional integrity and vascular barrier function.—Liu, F., Schaphorst, K. L., Verin, A. D., Jacobs, K., Birukova, A., Day, R. M., Bogatcheva, N., Bottaro, D. P., Garcia, J. G. N. Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3ß.
Key Words: ß-catenin • MAP kinases • endothelial permeability • cytoskeleton • transendothelial electrical resistance
This article has been cited by other articles:
|
|
 |
|
  L.-K. Meng and C.-G. Liu Gene therapies for pulmonary hypertension--from experimental trials to bedside aspects Eur. J. Cardiothorac. Surg., February 1, 2010; 37(2): 407 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Ramirez, S. Fan, M. Zhang, A. Papugani, N. Reichenbach, H. Dykstra, A. J. Mercer, R. F. Tuma, and Y. Persidsky Inhibition of Glycogen Synthase Kinase 3{beta} (GSK3{beta}) Decreases Inflammatory Responses in Brain Endothelial Cells Am. J. Pathol., February 1, 2010; 176(2): 881 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Meyer, Y. Huang, P. A. Singleton, S. Sammani, J. Moitra, C. L. Evenoski, A. N. Husain, S. Mitra, L. Moreno-Vinasco, J. R. Jacobson, et al. GADD45a is a novel candidate gene in inflammatory lung injury via influences on Akt signaling FASEB J, May 1, 2009; 23(5): 1325 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Johnson TNF-induced activation of pulmonary microvessel endothelial cells: a role for GSK3{beta} Am J Physiol Lung Cell Mol Physiol, April 1, 2009; 296(4): L700 - L709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Birukova, I. Cokic, N. Moldobaeva, and K. G. Birukov Paxillin Is Involved in the Differential Regulation of Endothelial Barrier by HGF and VEGF Am. J. Respir. Cell Mol. Biol., January 1, 2009; 40(1): 99 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Md. R. Abid, R. J. Nadeau, K. C. Spokes, T. Minami, D. Li, S.-C. Shih, and W. C. Aird Hepatocyte Growth Factor Inhibits VEGF-Forkhead-Dependent Gene Expression in Endothelial Cells Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 2042 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chen, S. Pendyala, V. Natarajan, J. G. N. Garcia, and J. R. Jacobson Endothelial cell barrier protection by simvastatin: GTPase regulation and NADPH oxidase inhibition Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L575 - L583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, N. Moldobaeva, J. Xing, and K. G. Birukov Magnitude-dependent effects of cyclic stretch on HGF- and VEGF-induced pulmonary endothelial remodeling and barrier regulation Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L612 - L623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Troyanovsky, D. F. Alvarez, J. A. King, and K. L. Schaphorst Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L266 - L275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Singleton, R. Salgia, L. Moreno-Vinasco, J. Moitra, S. Sammani, T. Mirzapoiazova, and J. G. N. Garcia CD44 Regulates Hepatocyte Growth Factor-mediated Vascular Integrity: ROLE OF c-Met, Tiam1/Rac1, DYNAMIN 2, AND CORTACTIN J. Biol. Chem., October 19, 2007; 282(42): 30643 - 30657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, E. Alekseeva, A. Mikaelyan, and K. G. Birukov HGF attenuates thrombin-induced endothelial permeability by Tiam1-mediated activation of the Rac pathway and by Tiam1/Rac-dependent inhibition of the Rho pathway FASEB J, September 1, 2007; 21(11): 2776 - 2786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Miyahara, K. Hamanaka, D. S. Weber, D. A. Drake, M. Anghelescu, and J. C. Parker Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L11 - L21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, I. Malyukova, V. Poroyko, and K. G. Birukov Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L199 - L211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Morrow, C. Sweeney, Y. A. Birney, S. Guha, N. Collins, P. M. Cummins, R. Murphy, D. Walls, E. M. Redmond, and P. A. Cahill Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo Am J Physiol Cell Physiol, January 1, 2007; 292(1): C488 - C496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Moy, K. Blackwell, M. H. Wu, and H. J. Granger Growth factor- and heparin-dependent regulation of constitutive and agonist-mediated human endothelial barrier function Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2126 - H2135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Biswas, S. Canosa, D. Schoenfeld, J. Schoenfeld, P. Li, L. C. Cheas, J. Zhang, A. Cordova, B. Sumpio, and J. A. Madri PECAM-1 Affects GSK-3{beta}-Mediated {beta}-Catenin Phosphorylation and Degradation Am. J. Pathol., July 1, 2006; 169(1): 314 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Clermont, M. Cahill, H. Salti, S. L. Rook, C. Rask-Madsen, L. Goddard, J. S. Wong, D. Bursell, S. E. Bursell, and L. P. Aiello Hepatocyte Growth Factor Induces Retinal Vascular Permeability via MAP-Kinase and PI-3 Kinase without Altering Retinal Hemodynamics. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2701 - 2708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, S. Chatchavalvanich, A. Rios, K. Kawkitinarong, J. G.N. Garcia, and K. G. Birukov Differential Regulation of Pulmonary Endothelial Monolayer Integrity by Varying Degrees of Cyclic Stretch Am. J. Pathol., May 1, 2006; 168(5): 1749 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Wilkes, T. M. Egan, and H. Y. Reynolds Lung Transplantation: Opportunities for Research and Clinical Advancement Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 944 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Singleton, S. M. Dudek, E. T. Chiang, and J. G. N. Garcia Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and {alpha}-actinin FASEB J, October 1, 2005; 19(12): 1646 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Jia, L. Barbier, H. Stuart, M. Amraei, S. Pelech, J. W. Dennis, P. Metalnikov, P. O'Donnell, and I. R. Nabi Tumor Cell Pseudopodial Protrusions: LOCALIZED SIGNALING DOMAINS COORDINATING CYTOSKELETON REMODELING, CELL ADHESION, GLYCOLYSIS, RNA TRANSLOCATION, AND PROTEIN TRANSLATION J. Biol. Chem., August 26, 2005; 280(34): 30564 - 30573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Smyth and H. J.M. Brady cMet and Fas Receptor Interaction Inhibits Death-Inducing Signaling Complex Formation in Endothelial Cells Hypertension, July 1, 2005; 46(1): 100 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Jacobson, J. W. Barnard, D. N. Grigoryev, S.-F. Ma, R. M. Tuder, and J. G. N. Garcia Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1026 - L1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Finigan, S. M. Dudek, P. A. Singleton, E. T. Chiang, J. R. Jacobson, S. M. Camp, S. Q. Ye, and J. G. N. Garcia Activated Protein C Mediates Novel Lung Endothelial Barrier Enhancement: ROLE OF SPHINGOSINE 1-PHOSPHATE RECEPTOR TRANSACTIVATION J. Biol. Chem., April 29, 2005; 280(17): 17286 - 17293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Morrow, C. Sweeney, Y. A. Birney, P. M. Cummins, D. Walls, E. M. Redmond, and P. A. Cahill Cyclic Strain Inhibits Notch Receptor Signaling in Vascular Smooth Muscle Cells In Vitro Circ. Res., March 18, 2005; 96(5): 567 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawkitinarong, L. Linz-McGillem, K. G. Birukov, and J. G. N. Garcia Differential Regulation of Human Lung Epithelial and Endothelial Barrier Function by Thrombin Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 517 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Dudek, J. R. Jacobson, E. T. Chiang, K. G. Birukov, P. Wang, X. Zhan, and J. G. N. Garcia Pulmonary Endothelial Cell Barrier Enhancement by Sphingosine 1-Phosphate: ROLES FOR CORTACTIN AND MYOSIN LIGHT CHAIN KINASE J. Biol. Chem., June 4, 2004; 279(23): 24692 - 24700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Peng, P. M. Hassoun, S. Sammani, B. J. McVerry, M. J. Burne, H. Rabb, D. Pearse, R. M. Tuder, and J. G. N. Garcia Protective Effects of Sphingosine 1-Phosphate in Murine Endotoxin-induced Inflammatory Lung Injury Am. J. Respir. Crit. Care Med., June 1, 2004; 169(11): 1245 - 1251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Jacobson, S. M. Dudek, K. G. Birukov, S. Q. Ye, D. N. Grigoryev, R. E. Girgis, and J. G. N. Garcia Cytoskeletal Activation and Altered Gene Expression in Endothelial Barrier Regulation by Simvastatin Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 662 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Otte and D. K. Podolsky Functional modulation of enterocytes by gram-positive and gram-negative microorganisms Am J Physiol Gastrointest Liver Physiol, April 1, 2004; 286(4): G613 - G626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Pollack, G. Apodaca, and K. E. Mostov Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of tight junction functional integrity Am J Physiol Cell Physiol, March 1, 2004; 286(3): C482 - C494. [Abstract] [Full Text]
|
|
|
|
|
|
K. G. Birukov, J. R. Jacobson, A. A. Flores, S. Q. Ye, A. A. Birukova, A. D. Verin, and J. G. N. Garcia Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L785 - L797. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
