Cited by 186Connective Tissue Growth Factor ResearchCell Adhesion Molecules ResearchBone and Dental Protein Studies

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The Angiogenic Factor Cysteine-Rich 61 (CYR61, CCN1) Supports Vascular Smooth Muscle Cell Adhesion and Stimulates Chemotaxis through Integrin 6 1 and Cell Surface Heparan Sulfate Proteoglycans

Grzeszkiewicz, T. M.·2002·Endocrinology

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Abstract

Cysteine-rich 61 (CYR61, CCN1) is a heparin-binding, extracellular, matrix-associated protein of the cysteine-rich 61/nephroblastoma family, which also includes connective tissue growth factor, nephroblastoma overexpressed, Wnt-induced secreted protein-1 (WISP-1), WISP-2, and WISP-3. CYR61 induces angiogenesis in vivo and supports cell adhesion, promotes cell migration, and enhances growth factor-stimulated mitogenesis in fibroblasts and endothelial cells. Although the expression of CYR61 has been observed in arterial walls, its function in vascular smooth muscle cells (VSMCs) has not been examined to date. Here we show that purified CYR61 supports VSMC adhesion in a dose-dependent, saturable manner through integrin α6β1 with an absolute requirement of cell surface heparan sulfate proteoglycans. In addition, CYR61 induces VSMC chemotaxis, but not chemokinesis, through integrin α6β1 and heparan sulfate proteoglycans. Heparin-binding defective CYR61 mutants are unable to support VSMC adhesion but can still induce chemotaxis at a reduced level. Following balloon angioplasty in rat carotid artery, CYR61 protein level is elevated in the media and neointima of the injured vessel by d 4 post angioplasty, peaks from d 7 to 14, and remains high for at least 28 d. These data demonstrate the activities of CYR61 in VSMCs, identify the receptors that mediate its functions, and show that CYR61 is synthesized in arterial smooth muscle walls during proliferative restenosis. Together, these results implicate CYR61 as a novel factor that modulates the responses of VSMCs to vascular injury.

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Authors: Grzeszkiewicz, T. M.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Grzeszkiewicz, T. M.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2002-04-01
Volume: 143
Issue: 4
Pages: 1441-1450
ISSN: 0013-7227 (ISSN-L)
DOI: 10.1210/en.143.4.1441
OpenAlex: W4236222382
Cited by: 23
References: 0
Citations by year: 2025: 1 · 2023: 1 · 2012: 1
FWCI: 0.93
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
Keywords: CYR61, vascular smooth muscle cells, alpha6beta1 integrin, heparan sulfate proteoglycans, cell adhesion, chemotaxis, angiogenesis, balloon angioplasty, restenosis, neointima, vascular injury, heparin binding, extracellular matrix proteins

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The Angiogenic Factor Cysteine-Rich 61 (CYR61, CCN1) Supports Vascular Smooth Muscle Cell Adhesion and Stimulates Chemotaxis through Integrin 6 1 and Cell Surface Heparan Sulfate Proteoglycans

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