國家衛生研究院 NHRI:Item 3990099045/15537
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15537


    Title: Dual-specificity phosphatase 6 deficiency attenuates arterial-injury-induced intimal hyperplasia in mice
    Authors: Hamdin, CD;Wu, ML;Chen, CM;Ho, YC;Jiang, WC;Gung, PY;Ho, HH;Chuang, HC;Tan, TH;Yet, SF
    Contributors: Institute of Cellular and Systems Medicine;Immunology Research Center
    Abstract: In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration, while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 reduced IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1β, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased the levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs, whereas lack of DUSP6 maintained their high levels, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.
    Date: 2023-12-05
    Relation: International Journal of Molecular Sciences. 2023 Dec 05;24(24):Article number 17136.
    Link to: http://dx.doi.org/10.3390/ijms242417136
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001130961700001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85180722474
    Appears in Collections:[Shaw-Fang Yet] Periodical Articles
    [Huai-Chia Chuang] Periodical Articles
    [Tse-Hua Tan] Periodical Articles

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