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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31786

    標題: Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice
    作者: Chen, Po-Sheng
    Wang, Kuan-Chieh
    Chao, Ting-Hsing
    Chung, Hsing-Chun
    Tseng, Shi-Ya
    Luo, Chawn-Yau
    Shi, Guey-Yueh
    Wu, Hua-Lin
    Li, Yi-Heng
    貢獻者: Natl Cheng Kung Univ Hosp & Coll Med, Dept Internal Med
    Natl Cheng Kung Univ Hosp & Coll Med, Dept Biochem & Mol Biol
    Natl Cheng Kung Univ Hosp & Coll Med, Dept Surg
    Natl Cheng Kung Univ Hosp & Coll Med, Inst Clin Med
    Chia Nan Univ Pharm & Sci, Dept Tourism Management, Coll Recreat & Hlth Management
    關鍵字: Soluble Thrombomodulin
    Progenitor Cells
    日期: 2017-06-12
    上傳時間: 2018-11-30 15:56:42 (UTC+8)
    出版者: Nature Publishing Group
    摘要: Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced EC apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers, ATG13 and LC3, were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. In conclusion, treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice.
    關聯: Scientific Reports, v.7, pp.3284
    Appears in Collections:[觀光事業管理系(含溫泉所)] 期刊論文

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