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Cited by 75Connective Tissue Growth Factor ResearchGlaucoma and retinal disordersConnexins and lens biology

Comparison of Prostaglandin F2α, Bimatoprost (Prostamide), and Butaprost (EP2 Agonist) on Cyr61 and Connective Tissue Growth Factor Gene Expression

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Liang, Yanbin, Li, Chen, Guzman, Victor M., Evinger, Albert J., Protzman, Charles E., Krauss, Achim H.-P., Woodward, David F.·2003·Journal of Biological Chemistry
DOI 10.1074/jbc.m301009200
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Abstract

Connective tissue growth factor (CTGF) and Cyr61 (cysteine-rich angiogenic protein 61) are members of the CCN gene family that encode multifunctional, extracellular matrix-associated signaling proteins. Because the mechanism of action of certain anti-glaucoma drugs involves extracellular matrix remodeling of ocular ciliary muscle, with a resultant increase in drainage of aqueous humor from the eye, we compared the effects of three pharmacologically distinct ocular hypotensive agents on Cyr61 and CTGF gene expression. Thus, prostaglandin F2alpha (PGF2alpha) (FP receptor agonist), Butaprost (EP2 receptor agonist), and Bimatoprost (a prostamide) were compared. Using Affymetrix gene chip technology, we first identified that PGF2alpha dramatically up-regulated Cyr61 and CTGF mRNA expression in HEK 293/EBNA cells (hFP-HEK 293/EBNA). Northern blot further confirmed the Cyr61 and CTGF up-regulation is in a dose- and time-dependent manner. PGF2alpha-induced up-regulation of Cyr61 appeared to exclusively involve the Rho pathway, and up-regulation of CTGF was via multiple intracellular pathways. Because prostamide receptors are, to date, defined only at the pharmacological level, Bimatoprost effects on Cyr61 and CTGF were studied in the isolated feline iris sphincter preparation, a tissue highly responsive to prostamides. Both PGF2alpha and Bimatoprost up-regulated Cyr61 mRNA expression in the cat iris tissue. Only PGF2alpha up-regulated CTGF mRNA expression in the cat iris. Therefore, PGF2alpha and Bimatoprost appear to interact with different receptors populations in the cat iris, according to their markedly different effects on CTGF. Activation of prostaglandin EP2 receptors (Gs-coupled) also up-regulated Cyr61 but not CTGF mRNA expression in the isolated cat iris. Similar data were observed in human primary ciliary smooth muscle cells. Thus, despite quite different signal transduction pathways, FP receptor stimulation up-regulates CTGF and Cyr61. The prostamide analog Bimatoprost and an EP2-selective agonist affects only Cyr61.

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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 [36]

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Research works printed but not linked: 2

  1. Berglund, B. A., Boring, D. L., Howlett, A. C. (1999) in Eicosanoids and Other Bioabtive Lipids in Cancer, Inflammation, and Radiation Research (Honn, K. V., Nigam, S., Marnett, L. J., and Walder, T. R., eds) Vol. 4, pp. 527-533, Kluwer Academic Publishers/Plenum Publishing Corp., New York
  2. Richter, M., Krauss, A. H.-P., Woodward, D. F., and Lu ¨tjen-Drecoll, E. (2003) Invest. Ophthalmol. Vis. Sci., in press

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Authors
Liang, Y., Li, C., Guzman, V. M., Evinger, A. J., Protzman, C. E., Krauss, A. H.-P., & Woodward, D. F.
Affiliations
Allergan (United States) (US)
Corresponding author
Woodward, David F.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-07
Volume
278
Issue
29
Pages
27267-27277
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m301009200
OpenAlex
W2139833082
Cited by
75
References
37
Citations by year
2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 3
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords
CYR61, connective tissue growth factor, prostaglandin F2alpha, bimatoprost, butaprost, prostamide, EP2 receptor agonist, FP receptor, ocular hypotensive agents, glaucoma medications, extracellular matrix remodeling, ciliary muscle, iris sphincter, Rho pathway, gene expression regulation, signal transduction
MeSH terms
Bimatoprost, Alprostadil, Amides, Animals, Cats, Cell Line, Cells, Cultured, Ciliary Body, Cloprostenol, Glaucoma, Humans, Iris, Kinetics, Lipids, Promoter Regions, Genetic, RNA, Messenger, Trabecular Meshwork, Dinoprost, Signal Transduction, Up-Regulation, Gene Expression, Immediate-Early Proteins, Oligonucleotide Array Sequence Analysis, Intercellular Signaling Peptides and Proteins, Connective Tissue Growth Factor, Cysteine-Rich Protein 61, In Vitro Techniques

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