A novel STAT3 inhibitor negatively modulates platelet activation and aggregation
A novel STAT3 inhibitor negatively modulates platelet activation and aggregation
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一种新型 STAT3 抑制剂负向调节血小板活化和聚集
DOI：
10.1038/aps.2016.155
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发表时间：
2017-03
影响因子：
8.2
通讯作者：
Mao Xin-liang
中科院分区：
文献类型：
--
作者：
Xu Zhuan;Xu Yu-jia;Hao Ya-nan;Ren Li-jie;Zhang Zu-bin;Xu Xin;Cao Bi-yin;Dai Ke-sheng;Zhu Li;Fang Qi;Kong Yan;Mao Xin-liang
信号转导子和转录激活子3（STAT 3）在血小板功能中起关键作用。本研究旨在了解STAT 3抑制剂SC 99对血小板活化和聚集的影响。应用免疫印迹分析来测量SC 99对STAT 3信号通路的影响。使用ChronoLog聚集计评价血小板聚集。流式细胞仪用于评估在SC 99存在下的P-选择素表达。AlamarBlue和Annexin-V染色分别用于评价血小板活力和凋亡。应用荧光显微镜分析血小板铺展。SC 99抑制人血小板中JAK 2和STAT 3的磷酸化，但对AKT、p65或Src的磷酸化没有影响，所有这些都参与血小板活化。进一步的研究表明，SC 99以剂量依赖性方式抑制胶原蛋白和凝血酶诱导的人血小板聚集。SC 99抑制凝血酶诱导的P-选择素表达和纤维蛋白原与单个血小板的结合。此外，SC 99抑制血小板在纤维蛋白原上的铺展和由外向内信号传导介导的凝块收缩。SC 99抑制小鼠血小板聚集，但不显著延长出血时间。综上所述，本研究揭示了SC 99作为STAT 3抑制剂抑制血小板活化和聚集。这种药物可以被开发为一种有前途的治疗血栓性疾病。
The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively. A fluorescence microscope was applied to analyze platelet spreading. SC99 inhibited the phosphorylation of JAK2 and STAT3 in human platelets but had no effects on the phosphorylation of AKT, p65 or Src, all of which are involved in platelet activation. Further studies revealed that SC99 inhibited human platelet aggregation induced by collagen and thrombin in a dose-dependent manner. SC99 inhibited thrombin-induced P-selectin expression and fibrinogen binding to single platelets. Moreover, SC99 inhibited platelet spreading on fibrinogen and clot retraction mediated by outside-in signaling. SC99 inhibited platelet aggregation in mice but it did not significantly prolong the bleeding time. Taken together, the present study revealed that SC99 inhibited platelet activation and aggregation as a STAT3 inhibitor. This agent can be developed as a promising treatment for thrombotic disorders.
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影响因子：
32.4
作者：
GREENLUND, AC;MORALES, MO;SCHREIBER, RD
通讯作者：
SCHREIBER, RD
影响因子：
20.3
作者：
A. Oda;Y. Miyakawa;B. Druker;A. Ishida;K. Ozaki;H. Ohashi;M. Wakui;M. Handa;Kiyoaki Watanabe;S. Okamoto;Y. Ikeda
通讯作者：
A. Oda;Y. Miyakawa;B. Druker;A. Ishida;K. Ozaki;H. Ohashi;M. Wakui;M. Handa;Kiyoaki Watanabe;S. Okamoto;Y. Ikeda
DOI：
10.1016/j.bbrc.2013.12.001
发表时间：
2014-01
影响因子：
3.1
作者：
Chun-Ho Shih;Tin-Bin Chiang;Wen‐Jeng Wang
通讯作者：
Chun-Ho Shih;Tin-Bin Chiang;Wen‐Jeng Wang
影响因子：
20.3
作者：
Yi Wu;N. Asazuma;K. Satoh;Y. Yatomi;T. Takafuta;M. Berndt;Y. Ozaki
通讯作者：
Yi Wu;N. Asazuma;K. Satoh;Y. Yatomi;T. Takafuta;M. Berndt;Y. Ozaki
影响因子：
20.3
作者：
Yi Wu;N. Asazuma;K. Satoh;Y. Yatomi;T. Takafuta;M. Berndt;Y. Ozaki
通讯作者：
Yi Wu;N. Asazuma;K. Satoh;Y. Yatomi;T. Takafuta;M. Berndt;Y. Ozaki