Factor VIIa and Thrombin Induce the Expression of Cyr61 and Connective Tissue Growth Factor, Extracellular Matrix Signaling Proteins That Could Act as Possible Downstream Mediators in Factor VIIa·Tissue Factor-induced Signal Transduction
Open accessAbstract
Extracellular interactions of plasma clotting factor VIIa (FVIIa) with tissue factor (TF) on cell surfaces trigger the intracellular signaling events. At present, it is unclear how these signals influence phenotype. To elucidate this, we have used cDNA microarray technology to examine changes in transcriptional program in human fibroblasts in response to exposure to FVIIa. cDNA microarrays revealed that FVIIa binding to TF up-regulated the expression of Cyr61 and CTGF (connective tissue growth factor), the genes that encode extracellular matrix signaling proteins Cyr61 and CTGF, respectively. Northern blot analysis confirmed that FVIIa binding to TF markedly increased the expression of Cyr61 and CTGF in a time- and dose-dependent manner. FVIIa catalytic activity is required for the gene induction. In addition to FVIIa, thrombin also induced the expression of Cyr61 and CTGF. Hirudin abolished the thrombin-induced expression of these mRNAs but not the FVIIa-induced expression. FVIIa-induced expression of Cyr61 appears not to involve the currently known protease-activated receptors (PARs), whereas thrombin-induced expression involves the activation of PAR1 and possibly an additional PAR. Various intracellular signaling pathway inhibitors exhibited different inhibitory pattern on FVIIa and thrombin-induced up-regulation of Cyr61. Cyr61 and CTGF could act as downstream mediators of FVIIa x TF in affecting various biological processes.
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CCN1 is activated by agonists of G protein-coupled receptors such as thrombin, prostaglandins E2 and F2α, and sphingosine-1-phosphate.
“CCN1 is activated by agonists of G protein-coupled receptors (GPCRs) such as thrombin [34,35], prostaglandins E2 and F2α [33,36], and sphinogosine-1-phosphate [37].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [34]
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- Authors
- Pendurthi, U. R., Allen, K. E., Ezban, M., & Rao, L. V. M.
- Affiliations
- The University of Texas Health Science Center at Tyler (US)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Pendurthi, Usha R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 275
- Issue
- 19
- Pages
- 14632-14641
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2032093848
- Cited by
- 145
- References
- 52
- Citations by year
- 2023: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- factor VIIa, tissue factor, thrombin, CYR61, connective tissue growth factor, extracellular matrix signaling, gene expression regulation, protease-activated receptors, PAR1, hirudin, human fibroblasts, signal transduction
- MeSH terms
- Cell Line, Gene Expression Regulation, Growth Substances, Humans, Kinetics, RNA, Messenger, Thrombin, Transcription, Genetic, Signal Transduction, Transcriptional Activation, Factor VIIa, Extracellular Matrix Proteins, Immediate-Early Proteins, DNA, Complementary, Intercellular Signaling Peptides and Proteins, Connective Tissue Growth Factor, Cysteine-Rich Protein 61
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