Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/30990
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 16812/19099 (88%)
Visitors : 6323012      Online Users : 308
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/30990


    Title: Gamma-secretase Inhibitor Prevents Proliferation and Migration of Ductus Arteriosus Smooth Muscle Cells through the Notch3-HES1/2/5 Pathway
    Authors: Wu, Jiunn-Ren
    Yeh, Jwu-Lai
    Liou, Shu-Fen
    Dai, Zen-Kong
    Wu, Bin-Nan
    Hsu, Jong-Hau
    Contributors: Kaohsiung Med Univ, Coll Med, Grad Inst Med
    Kaohsiung Med Univ Hosp, Dept Pediat
    Kaohsiung Med Univ, Fac Med, Coll Med, Dept Pediat
    Kaohsiung Med Univ, Coll Med, Dept & Grad Inst Pharmacol
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Keywords: Ductus arteriosus
    Notch signaling
    remodeling
    hypertension
    Date: 2016
    Issue Date: 2018-01-18 11:39:21 (UTC+8)
    Publisher: Ivyspring Int Publ
    Abstract: Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn. We investigated the effects and underlying mechanisms of gamma-secretase inhibitor DAPT, a Notch signaling inhibitor on angiotensin II (Ang II)-induced proliferation and migration of DASMCs. Proliferation and migration of DASMCs cultured from neonatal Wistar rats were induced by Ang II, with or without DAPT pre-treatment. In addition, potential underlying mechanisms including cell cycle progression, Ca2+ influx, reactive oxygen species (ROS) production, signal transduction of MAPK and Akt, and Notch receptor with its target gene pathway were examined. We found that DAPT inhibited Ang II-induced DASMCs proliferation and migration dose dependently. DAPT also arrested the cell cycle progression in the G(0)/G(1)-phase, and attenuated calcium overload and ROS production caused by Ang II. Moreover, DAPT inhibited nuclear translocation of Notch3 receptor intracellular domain, with decreased expression of its down-stream genes including HES1, HES2 and HES5. Finally, Ang II-activated ERK1/2, JNK and Akt were also counteracted by DAPT. In conclusion, DAPT inhibits Ang II-induced DASMCs proliferation and migration. These effects are potentially mediated by decreased calcium influx, reduced ROS production, and down-regulation of ERK1/2, JNK and Akt, through the Notch3-HES1/2/5 pathway. Therefore, Notch signaling has a role in DA remodeling and may provide a target pathway for therapeutic intervention of PDA.
    Relation: International Journal of Biological Sciences, v.12 n.9, pp.1063-1073
    Appears in Collections:[Dept. of Pharmacy] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    index.html0KbHTML38View/Open


    All items in CNU IR are protected by copyright, with all rights reserved.


    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback