Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and β-catenin

被引:93
作者
Venkiteswaran, K
Xiao, KY
Summers, S
Calkins, CC
Vincent, PA
Pumiglia, K
Kowalczyk, AP
机构
[1] Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Emory Skin Dis Res Ctr, Atlanta, GA 30322 USA
[4] Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA
[5] Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2002年 / 283卷 / 03期
关键词
adherens junction; angiogenesis; Wnt signaling;
D O I
10.1152/ajpcell.00417.2001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
VE-cadherin is an endothelial-specific cadherin that plays a central role in vascular barrier function and angiogenesis. The cytoplasmic domain of VE-cadherin is linked to the cytoskeleton through interactions with the armadillo family proteins beta-catenin and plakoglobin. Growing evidence indicates that beta-catenin and plakoglobin play important roles in epithelial growth and morphogenesis. To test the role of these proteins in vascular cells, a replication-deficient retroviral system was used to express intercellular junction proteins and mutants in the human dermal microvascular endothelial cell line (HMEC-1). A mutant VE-cadherin lacking an adhesive extracellular domain disrupted endothelial barrier function and inhibited endothelial growth. In contrast, expression of exogenous plakoglobin or metabolically stable mutants of beta-catenin stimulated HMEC-1 cell growth, which suggests that the beta-catenin signaling pathway was active in HMEC-1 cells. This possibility was supported by the finding that a dominant-negative mutant of the transcription factor TCF-4, designed to inhibit beta-catenin signaling, also inhibited HMEC-1 cell growth. These observations suggest that intercellular junction proteins function as components of an adhesion and signaling system that regulates vascular barrier function and growth.
引用
收藏
页码:C811 / C821
页数:11
相关论文
共 64 条
[1]   HMEC-1 - ESTABLISHMENT OF AN IMMORTALIZED HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE [J].
ADES, EW ;
CANDAL, FJ ;
SWERLICK, RA ;
GEORGE, VG ;
SUMMERS, S ;
BOSSE, DC ;
LAWLEY, TJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (06) :683-690
[2]   DELAYED ASSEMBLY OF DESMOSOMES IN KERATINOCYTES WITH DISRUPTED CLASSIC-CADHERIN-MEDIATED CELL-ADHESION BY A DOMINANT-NEGATIVE MUTANT [J].
AMAGAI, M ;
FUJIMORI, T ;
MASUNAGA, T ;
SHIMIZU, H ;
NISHIKAWA, T ;
SHIMIZU, N ;
TAKEICHI, M ;
HASHIMOTO, T .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1995, 104 (01) :27-32
[3]  
Angst BD, 2001, J CELL SCI, V114, P629
[4]   Angiogenesis and the skin: A primer [J].
Arbiser, JL .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1996, 34 (03) :486-497
[5]   Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways [J].
Arbiser, JL ;
Moses, MA ;
Fernandez, CA ;
Ghiso, N ;
Cao, YH ;
Klauber, N ;
Frank, D ;
Brownlee, M ;
Flynn, E ;
Parangi, S ;
Byers, HR ;
Folkman, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (03) :861-866
[6]   VE-cadherin mediates endothelial cell capillary tube formation in fibrin and collagen gels [J].
Bach, TL ;
Barsigian, C ;
Chalupowicz, DG ;
Busler, D ;
Yaen, CH ;
Grant, DS ;
Martinez, J .
EXPERIMENTAL CELL RESEARCH, 1998, 238 (02) :324-334
[7]   The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation [J].
Beavon, IRG .
EUROPEAN JOURNAL OF CANCER, 2000, 36 (13) :1607-1620
[8]   The dual role of cytoskeletal anchor proteins in cell adhesion and signal transduction [J].
Ben-Ze'Ev, A .
ANTICANCER MOLECULES: STRUCTURE, FUNCTION, AND DESIGN, 1999, 886 :37-47
[9]   β-catenin, an inducer of uncontrolled cell proliferation and migration in malignancies, is localized in the cytoplasm of vascular endothelium during neovascularization after myocardial infarction [J].
Blankesteijn, WM ;
van Gijn, ME ;
Essers-Janssen, YPG ;
Daemen, MJAP ;
Smits, JFM .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (03) :877-883
[10]   FUNCTIONAL-PROPERTIES OF HUMAN VASCULAR ENDOTHELIAL CADHERIN (7B4/CADHERIN-5), AN ENDOTHELIUM-SPECIFIC CADHERIN [J].
BREVIARIO, F ;
CAVEDA, L ;
CORADA, M ;
MARTINPADURA, I ;
NAVARRO, P ;
GOLAY, J ;
INTRONA, M ;
GULINO, D ;
LAMPUGNANI, MG ;
DEJANA, E .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1995, 15 (08) :1229-1239