國家衛生研究院 NHRI:Item 3990099045/14055

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Title:	Dual specificity phosphatase 6 promotes vascular smooth muscle cell proliferation in response to inflammatary stimulation and vascular injury
Authors:	Jiang, WC;Wu, ML;Yet, SF
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	Background and Aims: Dual-specificity phosphatases (DUSPs) are protein phosphatases that dephosphorylate tyrosine or serine/threonine residues. DUSP6 dephosphorylates MAPKs in the MAPK pathway, particularly ERK1/2. DUSP6 has been shown to play a critical role in the cellular processes in the heart, diet-induced obesity, T cell differentiation, and endothelial inflammation. However, the functions of DUSP6 in other vascular cells remain to be elucidated. Our goal is to investigate the role of DUSP6 in vascular smooth muscle cells (VSMCs) and in vascular disease.Methods: To examine whether DUSP6 has a role in vascular disease, we performed mouse guide wire injury model. Control and injured arteries were harvested at different time points for histological analysis to asses neointima formation and DUSP6 expression. To evaluate the role of DUSP6 in VSMC proliferation, which contributes to intimal hyperplasia, we performed knockdown and overexpression experiments in VSMCs with or without inflammatory cytokine stimulation. Proliferative activity and ERK1/2 activation were then measured.Results: Immunohistochemistry revealed low level of DUSP6 in normal mouse arteries. In response to injury, DUSP6 expression was increased in the neointima and media layer of the arteries. IL-1b induced DUSP6 level and proliferation in VSMCs. Overexpressing DUSP6 in VSMCs increased cellular proliferation while knocking down DUSP6 with siRNA abrogated IL-1b-induced proliferation. IL-1b-induced ERK1/2 activation preceded DUSP6 induction in VSMCs. Furthermore, ERK1/2 inhibitor abrogated IL-1β-induced ERK1/2 phosphorylation, DUSP6 induction, and VSMC proliferation. Conclusions: Taken together, our results indicate that DUSP6 induction promotes VSMC proliferation and vascular remodeling. DUSP6 might be a therapeutic target for occlusive vascular disease.
Date:	2020-12-01
Relation:	Atherosclerosis. 2020 Dec;315:E32.
Link to:	http://dx.doi.org/10.1016/j.atherosclerosis.2020.10.108
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9150&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000748958900090
Appears in Collections:	[Shaw-Fang Yet] Conference Papers/Meeting Abstract

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