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Cited by 61Connective Tissue Growth Factor ResearchAngiogenesis and VEGF in CancerWound Healing and Treatments

Promoter Function of the Angiogenic Inducer Cyr61Gene in Transgenic Mice: Tissue Specificity, Inducibility During Wound Healing, and Role of the Serum Response Element

Latinkic, B. V.·2001·Endocrinology
DOI 10.1210/en.142.6.2549
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Abstract

The cysteine-rich angiogenic protein 61 (Cyr61) is an extracellular matrix-associated, heparin-binding protein that mediates cell adhesion, stimulates cell migration, and enhances growth factor-induced cell proliferation. Cyr61 also promotes chondrogenic differentiation and induces neovascularization. In this study, we show that a 2-kb fragment of the Cyr61 promoter, which confers growth factor-inducible expression in cultured fibroblasts, is able to drive accurate expression of the reporter gene lacZ in transgenic mice. Thus, transgene expression was observed in the developing placenta and embryonic cardiovascular, skeletal, and central and peripheral nervous systems. The sites of transgene expression are consistent with those observed of the endogenous Cyr61 gene as determined by in situ hybridization and immunohistochemistry. The transgene expression in the cardiovascular system does not require the serum response element, a promoter sequence essential for transcriptional activation of Cyr61 by serum growth factors in cultured fibroblasts. Because the serum response element contains the CArG box, a sequence element implicated in cardiovascular-specific gene expression, the nonessential nature of this sequence for cardiovascular expression of Cyr61 is unexpected. Furthermore, the Cyr61 promoter-driven lacZ expression is inducible in granulation tissue during wound healing, as is synthesis of the endogenous Cyr61 protein, suggesting a role for Cyr61 in wound healing. Consistent with this finding, purified Cyr61 protein promotes the healing of a wounded fibroblast monolayer in culture. In addition, we mapped the mouse Cyr61 gene to the distal region of chromosome 3. Together, these results define the functional Cyr61 promoter in vivo, and suggest a role of Cyr61 in wound healing through its demonstrated angiogenic activities upon endothelial cells and its chemotactic and growth promoting activities upon fibroblasts.

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  • A 2 kb Ccn1 promoter fragment including the SRE is sufficient to confer accurate developmental and tissue-specific expression in transgenic mice when linked to β-galactosidase, defining the functional Ccn1 promoter for in vivo transcriptional regulation.

    “A 2 kb Ccn1 promoter fragment that includes the SRE is sufficient to confer accurate developmental and tissue-specific expression in transgenic mice when linked to the β-galactosidase gene as a reporter, thus defining the functional Ccn1 promoter for transcriptional regulation in vivo [40].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [40]

  • CCN1 is highly expressed in hypertrophic cartilage at the growth plate at later stages of skeletal development.

    “At later stages of skeletal development, CCN1 is highly expressed in the hypertrophic cartilage at the growth plate [40].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [40]

  • In cutaneous wound healing, Ccn1 is highly expressed in myofibroblasts of granulation tissue.

    “In cutaneous wound healing, Ccn1 is highly expressed in myofibroblasts of the granulation tissue [40,87].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [40]

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Authors
Latinkic, B. V.
Affiliations
University of Illinois Chicago (US)
ORCID
Latinkic, B. V.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2001-06-01
Volume
142
Issue
6
Pages
2549-2557
ISSN
0013-7227 (ISSN-L)
DOI
10.1210/en.142.6.2549
OpenAlex
W2087930852
Cited by
61
References
45
Citations by year
2022: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2015: 4 · 2014: 2 · 2013: 5
FWCI
2.56
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
  • U.S. Department of Health and Human Services
  • Small Business Innovation Research
  • National Institutes of Health
  • National Cancer Institute (R01CA046565, CA52220, CA78044, CA-46565, R01CA052220)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
CYR61, promoter activity, transgenic mice, lacZ reporter, tissue specificity, serum response element, CArG box, wound healing, granulation tissue, angiogenesis, neovascularization, fibroblast migration, embryonic development, placenta, extracellular matrix
MeSH terms
Animals, beta-Galactosidase, Chromosome Mapping, Crosses, Genetic, Fibroblasts, Growth Substances, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Promoter Regions, Genetic, Wound Healing, Gene Expression, In Situ Hybridization, Immediate-Early Proteins, Neovascularization, Physiologic, Response Elements, Intercellular Signaling Peptides and Proteins, Mice, Cysteine-Rich Protein 61

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