Comparison of Prostaglandin F2α, Bimatoprost (Prostamide), and Butaprost (EP2 Agonist) on Cyr61 and Connective Tissue Growth Factor Gene Expression
| Autor: | Victor M. Guzman, Yanbin Liang, Albert J. Evinger, Charles E. Protzman, Chen Li, David F. Woodward, Achim H.-P. Krauss |
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| Rok vydání: | 2003 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Prostaglandin E2 receptor Gene Expression Iris Prostaglandin In Vitro Techniques Biology Dinoprost Biochemistry Cell Line Immediate-Early Proteins chemistry.chemical_compound Trabecular Meshwork Internal medicine medicine Animals Humans RNA Messenger Alprostadil Promoter Regions Genetic Receptor Molecular Biology Cells Cultured Oligonucleotide Array Sequence Analysis integumentary system Bimatoprost Ciliary Body Connective Tissue Growth Factor Cloprostenol Glaucoma Cell Biology Amides Lipids Up-Regulation Cell biology CTGF Kinetics Endocrinology chemistry CYR61 Cats Intercellular Signaling Peptides and Proteins Signal transduction Cysteine-Rich Protein 61 Signal Transduction medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 278:27267-27277 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m301009200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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