國家衛生研究院 NHRI:Item 3990099045/1487

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Title:	Synergistic roles of platelet-derived growth factor-BB and interleukin-1 beta in phenotypic modulation of human aortic smooth muscle cells
Other Titles:	Synergistic roles of platelet-derived growth factor-BB and interleukin-1β in phenotypic modulation of human aortic smooth muscle cells
Authors:	Chen, CN;Li, YSJ;Yeh, YT;Lee, PL;Usami, S;Chien, S;Chiu, JJ
Contributors:	Division of Medical Engineering Research
Abstract:	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-1 beta). Human aortic SMCs grown on polymerized collagen showed high expression levels of contractile markers (smooth muscle alpha-actin, myosin heavy chain, and calponin). These levels were not significantly affected by PDGF-BB and IL-1 beta individually, but decreased markedly after the combined usage of PDGF-BB and IL-1 beta. PDGF/IL-1 beta costirinulation also induced a sustained phosphorylation of Akt and p70 ribosomal S6 kinase (p70S6K). The effects of PDGF/IL-1 beta 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-10 induced a sustained phosphorylation of PDGF receptor (PDGFR)-beta and its association with IL-1 receptor (IL-1R1). Such activation and association of receptors were blocked by a PDGFR-beta neutralizing antibody (AF385), an IL-1R1 antagonist (IL-1 ra), as well as a specific inhibitor of PDGFR-beta phosphorylation (AG1295); these agents also eliminated the PDGF-BB/IL-1 beta-induced signaling and phenotypic modulation. PDGF-BB/IL-1 beta inhibited the polymerized collagen-induced serum response factor DNA binding activity in the nucleus, and this effect was mediated by the PDGFR-beta/IL-1R1 association and phosphaticlylinositol 3-kinase/Akt/p70S6K pathway. Our findings provide insights into the mechanism of SMC phenotypic modulation from contractile to synthetic, e.g., in atherosclerosis.
Keywords:	Multidisciplinary Sciences
Date:	2006-02-21
Relation:	Proceedings of the National Academy of Sciences of the United States of America. 2006 Feb;103(8):2665-2670.
Link to:	http://dx.doi.org/10.1073/pnas.0510973103
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000235554900035
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33644504832
Appears in Collections:	[Jeng-Jiann Chiu] Periodical Articles

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