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PMID: 10082563 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo.

Molecular and cellular biology ·Vol. 19 ·No. 4 ·1999-04-00 ·Pages 2958-66

Babic AM, Chen CC, Lau LF

Abstract

Fisp12 was first identified as a secreted protein encoded by a growth factor-inducible immediate-early gene in mouse fibroblasts, whereas its human ortholog, CTGF (connective tissue growth factor), was identified as a mitogenic activity in conditioned media of human umbilical vein endothelial cells. Fisp12/CTGF is a member of a family of secreted proteins that includes CYR61, Nov, Elm-1, Cop-1/WISP-2, and WISP-3. Fisp12/CTGF has been shown to promote cell adhesion and mitogenesis in both fibroblasts and endothelial cells and to stimulate cell migration in fibroblasts. These findings, together with the localization of Fisp12/CTGF in angiogenic tissues, as well as in atherosclerotic plaques, suggest a possible role for Fisp12/CTGF in the regulation of vessel growth during development, wound healing, and vascular disease. In this study, we show that purified Fisp12 (mCTGF) protein promotes the adhesion of microvascular endothelial cells through the integrin receptor alphavbeta3. Furthermore, Fisp12 stimulates the migration of microvascular endothelial cells in culture, also through an integrin-alphavbeta3-dependent mechanism. In addition, the presence of Fisp12 promotes endothelial cell survival when cells are plated on laminin and deprived of growth factors, a condition that otherwise induces apoptosis. In vivo, Fisp12 induces neovascularization in rat corneal micropocket implants. These results demonstrate that Fisp12 is a novel angiogenic inducer and suggest a direct role for Fisp12 in the adhesion, migration, and survival of endothelial cells during blood vessel growth. Taken together with the recent finding that the related protein CYR61 also induces angiogenesis, we suggest that Fisp12/mCTGF and CYR61 comprise prototypes of a new family of angiogenic regulators that function, at least in part, through integrin-alphavbeta3-dependent pathways.

MeSH Terms
Animals Cell Adhesion Cell Movement Cell Survival Connective Tissue Growth Factor Cornea/blood supply Endothelium, Vascular/cytology,physiology Growth Substances/metabolism Humans Immediate-Early Proteins/metabolism Intercellular Signaling Peptides and Proteins Neovascularization, Physiologic Nephroblastoma Overexpressed Protein Rats Receptors, Vitronectin/metabolism
Chemicals
CCN2 protein, human CCN2 protein, mouse CCN2 protein, rat CCN3 protein, human Ccn3 protein, mouse Growth Substances Immediate-Early Proteins Intercellular Signaling Peptides and Proteins Nephroblastoma Overexpressed Protein Receptors, Vitronectin Connective Tissue Growth Factor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Babic A M
Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60607-7170, USA.
Chen C C
Lau L F
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.4.2958
Published
1999-04-00
Pages
2958-66
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84090
Subset
IM
Grants
NCI NIH HHS · R01 CA046565 · United States
NCI NIH HHS · CA46565 · United States
NCI NIH HHS · CA80080 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.4.2958 PMC Full Text View journal details
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