Regulatory effects of platelet-derived growth factor-AA homodimer on migration of vascular smooth muscle cells
書誌事項
- 公開日
- 1992-11
- 権利情報
-
- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- http://creativecommons.org/licenses/by/4.0/
- DOI
-
- 10.1016/s0021-9258(18)50019-3
- 公開者
- Elsevier BV
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説明
Migration of medial smooth muscle cells (SMC) into the intima is important in intimal thickening of atherosclerotic tissues. To study the functions of three isoforms of platelet-derived growth factor (PDGF) in atherosclerosis, we investigated their effects on SMC migration by Boyden's chamber method. Although PDGF-AB and PDGF-BB enhanced SMC migration dose-dependently, PDGF-AA did not enhance SMC migration, but instead inhibited SMC migration induced by PDGF-AB or PDGF-BB. PDGF-AA also inhibited SMC migration induced by two other migration factors, fibronectin and SMC-derived migration factor. PDGF-AA is considered to be coexpressed with transforming growth factor (TGF)-beta 1 in atherosclerotic tissues. Treatment of SMC with TGF-beta 1 reduced an autocrine migration activity from SMC. Studies using anti-PDGF antibody revealed that an increased secretion of PDGF-AA by TGF-beta 1 caused the reduced migration activity. cAMP increase by forskolin and dibutyryl cAMP suppressed SMC migration, whereas cAMP decrease by pertussis toxin had no effects on PDGF-AA-suppressed migration. In contrast, staurosporine, an inhibitor of protein kinase C, enhanced SMC migration and neutralized the inhibitory effect of PDGF-AA. These findings suggest that PDGF-AA regulates SMC migration in intimal thickening in atheroma formation and that protein kinase C may play an important role in the inhibitory mechanism of PDGF-AA.
収録刊行物
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- Journal of Biological Chemistry
-
Journal of Biological Chemistry 267 (32), 22806-22812, 1992-11
Elsevier BV
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キーワード
- Platelet-Derived Growth Factor
- Dose-Response Relationship, Drug
- Macromolecular Substances
- Colforsin
- Aorta, Thoracic
- Isoquinolines
- Muscle, Smooth, Vascular
- Piperazines
- Fibronectins
- Biological Factors
- Kinetics
- Alkaloids
- Bucladesine
- Pertussis Toxin
- Cell Movement
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
- Cyclic AMP
- Animals
- Cell Division
- Cells, Cultured