Synergistic roles of platelet-derived growth factor-BB and interleukin-1β in phenotypic modulation of human aortic smooth muscle cells

Cheng Nan Chen, Yi Shuan J. Li, Yi Ting Yeh, Pei Ling Lee, Shunichi Usami, Shu Chien, Jeng Jiann Chiu

研究成果: 雜誌貢獻文章同行評審

70 引文 斯高帕斯(Scopus)

摘要

The phenotype of smooth muscle cells (SMCs) plays an important role in vascular function in health and disease. We investigated the mechanism of modulation of SMC phenotype (from contractile to synthetic) induced by the synergistic action of a growth factor (platelet-derived growth factor, PDGF-BB) and a cytokine (interleukin, IL-1β). Human aortic SMCs grown on polymerized collagen showed high expression levels of contractile markers (smooth muscle α-actin, myosin heavy chain, and calponin). These levels were not significantly affected by PDGF-BB and IL-1β individually, but decreased markedly after the combined usage of PDGF-BB and IL-1β. PDGF/IL-1β costimulation also induced a sustained phosphorylation of Akt and p70 ribosomal 56 kinase (p70S6K). The effects of PDGF/IL-1β costimulation on contractile marker expression and Akt and p70S6K phosphorylation were blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 and by adenovirus expressing a dominant-negative Akt, and they were mimicked by constitutively active Akt. PDGF-BB/ IL-1β induced a sustained phosphorylation of PDGF receptor (PDGFR)-β and its association with IL-1 receptor (IL-1R1). Such activation and association of receptors were blocked by a PDGFR-β neutralizing antibody (AF385), an IL-1R1 antagonist (IL-1ra), as well as a specific inhibitor of PDGFR-β phosphorylation (AG1295); these agents also eliminated the PDGF-BB/IL-1β-induced signaling and phenotypic modulation. PDGF-BB/IL-1β inhibited the polymerized collagen-induced serum response factor DNA binding activity in the nucleus, and this effect was mediated by the PDGFR-β/IL-1R1 association and phosphatidylinositol 3-kinase Akt p70S6K pathway. Our findings provide insights into the mechanism of SMC phenotypic modulation from contractile to synthetic, e.g., in atherosclerosis.

原文英語
頁(從 - 到)2665-2670
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
103
發行號8
DOIs
出版狀態已發佈 - 二月 21 2006
對外發佈Yes

ASJC Scopus subject areas

  • General

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