國家衛生研究院 NHRI:Item 3990099045/12858
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 914518      線上人數 : 1380
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/12858


    題名: WNK1-OSR1/SPAK kinase cascade is important for angiogenesis
    作者: Huang, CL;Jian, X;Yuh, CH
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: WNK [with-no-lysine (K)] kinases are a family of four members of serine and threonine kinases that regulate renal Na(+) and K(+) transport. Mutations of WNK1 and WNK4 cause a hereditary hypertensive and hyperkalemic disease known as pseudohypoaldosteronism type II (PHA2). Unlike other WNK isoforms, WNK1 is ubiquitously expressed and regulates many other cellular processes outside the kidney. Oxidative stress response kinase (OSR1) and related STE 20/SPS1-related proline alanine-rich kinase (SPAK) are downstream kinases of WNK kinases. To examine the role of WNK kinase cascade in vivo, we generated global Wnk1-deleted mice and found that Wnk1-ablated mice die in utero from embryonic angiogenesis and cardiac developmental defects. Endothelial-specific Wnk1 deletion reveals that angiogenesis defect is due to WNK1 requirement in endothelium. We further showed that global and endothelial-deletion of Osr1 phenocopies Wnk1 deletion. Furthermore, expression of a catalytic constitutively active Osr1 transgene rescues angiogenesis defects and embryonic lethality of Wnk1-ablated mice. In zebrafish, Wnk1 knockdown causes similar angiogenesis defects to Vegf2 (Flk1) knockdown and that expression of WNK1 partially rescues Flk1 angiogenesis defects. The results indicate that WNK1 is downstream of VEGF signaling cascade. T-lymphocytes isolated from Wnk1-null mice exhibit migration defects. Inhibition of WNK1-OSR1 downstream target Na-K-2Cl cotransporter NKCC1 mimics migration defect of WNK1-deficient T-lymphocytes. Thus, WNK1-OSR1/SPAK cascade is important for angiogenesis. Regulation of ion homeostasis and cell volume may underlie the mechanism for WNK1 regulation of endothelial cell migration and angiogenesis.
    日期: 2020-07-18
    關聯: Transactions of the American Clinical and Climatological Association. 2020 Jul;131:140-146.
    Link to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358493/
    顯示於類別:[喻秋華] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    PUB32675854.pdf562KbAdobe PDF261檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

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