1α,25-Dihydroxyvitamin D 3 Induces Vascular Smooth Muscle Cell Migration via Activation of Phosphatidylinositol 3-Kinase
| Autor: | Jianxin Sun, Michela C. Rebsamen, Anthony W. Norman, James K. Liao |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Physiology Sialoglycoproteins medicine.medical_treatment Blotting Western Biology Muscle Smooth Vascular Rats Sprague-Dawley Wortmannin Phosphatidylinositol 3-Kinases chemistry.chemical_compound Calcitriol Cell Movement Ergosterol Internal medicine Cell Adhesion medicine Animals LY294002 Phosphatidylinositol Enzyme Inhibitors Cells Cultured Dose-Response Relationship Drug Kinase Biological activity Molecular biology Rats Enzyme Activation Steroid hormone Endocrinology chemistry Osteopontin RNA Polymerase II Signal transduction Cardiology and Cardiovascular Medicine Dichlororibofuranosylbenzimidazole |
| Zdroj: | Circulation Research. 91:17-24 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000025269.60668.0f |
| Popis: | The steroid hormone 1α,25-dihydroxyvitamin D 3 [1α, 25-(OH) 2 D 3 ] promotes vascular smooth muscle cell (VSMC) growth and calcification, but the precise mechanism by which 1α, 25-(OH) 2 D 3 regulates VSMC migration is unknown. In rat aortic SMCs, we found that 1α, 25-(OH) 2 D 3 (0.1 to 100 nmol/L) induced a dose-dependent increase in VSMC migration. This response required the activation of phosphatidylinositol 3-kinase (PI3 kinase) because 1α, 25-(OH) 2 D 3 -induced migration was completely abolished by the PI3 kinase inhibitors, LY294002 (10 μmol/L) or wortmannin (30 nmol/L). Furthermore, the RNA polymerase inhibitor, 5,6-dichlorobenzimidazole riboside (50 μmol/L), did not affect 1α, 25-(OH) 2 D 3 -induced VSMC migration, suggesting that gene transcription is not involved in this rapid response. Using analogs of 1α, 25-(OH) 2 D 3 , which have been characterized for their abilities to induce either transcriptional or nontranscriptional responses of 1α, 25-(OH) 2 D 3 , we found that 1α,25-dihydroxylumisterol, which is a potent agonist of the rapid, nongenomic responses, was equipotent with 1α, 25-(OH) 2 D 3 in inducing PI3 kinase activity and VSMC migration. Moreover, 1β, 25-(OH) 2 D 3 , which specifically antagonizes the nongenomic actions of 1α, 25-(OH) 2 D 3 , abolished 1α, 25-(OH) 2 D 3 -induced PI3 kinase activity and VSMC migration, whereas the inhibitor of the genomic actions of vitamin D, (23S)-25-dehydro-1α-OH-D 3 -26,23-lactone, did not affect these responses. These results indicate that 1α, 25-(OH) 2 D 3 induces VSMC migration independent of gene transcription via PI3 kinase pathway, and suggest a possible mechanism by which 1α, 25-(OH) 2 D 3 may contribute to neointima formation in atherosclerosis and vascular remodeling. |
| Databáze: | OpenAIRE |
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