Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/21574
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    標題: Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells
    作者: Hua-Lin Wu
    Chi-Iou Lin
    Yuan-Li Huang
    Pin-Shern Chen
    Cheng-Hsiang Kuo
    Mei-Shing Chen
    Georgiana Cho-Chen Wu
    Guey-Yueh Shi
    Hsi-Yuan Yang
    Hsinyu Le
    貢獻者: 生物科技系
    關鍵字: Thrombomodulin
    Lysophosphatidic acid
    Endothelial cells
    日期: 2008-02
    上傳時間: 2009-07-21 14:07:03 (UTC+8)
    出版者: Elsevier
    摘要: Thrombomodulin (TM) is an anticoagulant glycoprotein highly expressed on endothelial cell surfaces. Increased levels of soluble TM in circulation have been widely accepted as an indicator of endothelial damage or dysfunction. Previous studies indicated that various proinflammatory factors stimulate TM shedding in various cell types such as smooth muscle cells and epithelial cells. Lysophosphatidic acid (LPA) is a bioactive lipid mediator present in biological fluids during endothelial damage or injury. In the present study, we first observed that LPA triggered TM shedding in human umbilical vein endothelial cells (HUVECs). By Cyflow analysis, we showed that the LPA-induced accessibility of antibodies to the endothelial growth factor (EGF)-like domain of TM is independent of matrix metalloproteinases (MMPs), while LPA-induced TM lectin-like domain shedding is MMP-dependent. Furthermore, a stable cell line expressing TM without its lectin-like domain exhibited a higher cell proliferation rate than a stable cell line expressing full-length TM. These results imply that LPA induces TM lectin-like domain shedding, which might contribute to the exposure of its EGF-like domain for EGF receptor (EGFR) binding, thereby stimulating subsequent cell proliferation. Based on our findings, we propose a novel mechanism for the exposure of TM EGF-like domain, which possibly mediates LPA-induced EGFR transactivation.
    關聯: Biochemical and biophysical research communications 367(1):p.162-168
    顯示於類別:[生物科技系(所)] 期刊論文

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