國家衛生研究院 NHRI:Item 3990099045/12511
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    题名: Dual-specificity phosphatase 6 deficiency protects against intimal hyperplasia after arterial injury
    作者: Yet, SF
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Dysregulation of MAPK activation cascades has been implicated in various diseases. Dual-specificity phosphatases (DUSPs) are a subfamily of protein tyrosine phosphatases that dephosphorylate MAPKs and modulate critical signaling pathways. Studies have shown that DUSP6 plays an important role in the heart and diet-induced obesity. However, the role of DUSP6 in vascular disease is largely unclear. Our goal is to investigate whether DUSP6 has a role in occlusive vascular disease. To this end, we used a neointima formation model by denuding endothelium of mouse femoral arteries with a guide wire. We showed that DUSP6 was expressed at very low levels in the normal uninjured mouse arteries; however, DUSP6 expression was increased in the arterial wall of injured blood vessels, suggesting a potential role of DUSP6 in vascular disease. Compared with wild-type mice, DUSP6 deficiency reduced neointima formation 4 weeks after arterial injury in mice. BrdU incorporation assays revealed that lack of DUSP6 resulted in decreased smooth muscle cell (SMC) proliferation in the neointima and media 2 weeks after injury, indicating DUSP6 may promote SMC proliferation in response to injury. Indeed, overexpressing DUSP6 in primary SMCs increased cellular proliferation, similar to that exerted by inflammatory cytokine IL-1β while knocking down DUSP6 expression with siRNA abrogated IL-1β-induced SMC proliferation. Pathway analysis showed that IL-1β-induced ERK1/2 activation preceded DUSP6 induction in SMCs. Intriguingly, ERK1/2 inhibitor U0126 abolished IL-1β-mediated ERK1/2 activation, DUSP6 induction, and SMC proliferation. Taken together, our results indicate that DUSP6 induction promotes vascular remodeling under pathological conditions. DUSP6 might be a therapeutic target for preventing/treating occlusive vascular disease.
    日期: 2019-08
    關聯: Circulation Research. 2019 Aug;125(Suppl. 1):Abstract number 777.
    Link to: https://doi.org/10.1161/res.125.suppl_1.777
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0009-7330&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000511467800460
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