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《医学前沿(英文)》 2016年 第10卷 第3期 页码 311-319 doi: 10.1007/s11684-016-0460-0
We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e., Tac-β3, Tac-β3D741, Tac-β3D747, Tac-β3D754, Tac-β3D759, and Tac-β3DNITY) consisting of the extracellular and transmembrane domains of human IL-2 receptor (Tac) and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin αIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3DNITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3D759, Tac-β3DNITY, and Tac-β3D754, but not Tac-β3D747 or Tac-β3D741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3 and Tac-β3DNITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3D759 and 123/Tac-β3D754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3D747 and 123/Tac-β3D741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.
关键词: integrin β3 signal transduction trans-dominant inhibition model
Talin and kindlin: the one-two punch in integrin activation
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《医学前沿(英文)》 2014年 第8卷 第1期 页码 6-16 doi: 10.1007/s11684-014-0317-3
Proper cell-cell and cell-matrix contacts mediated by integrin adhesion receptors are important for development, immune response, hemostasis and wound healing. Integrins pass trans-membrane signals bidirectionally through their regulated affinities for extracellular ligands and intracellular signaling molecules. Such bidirectional signaling by integrins is enabled by the conformational changes that are often linked among extracellular, transmembrane and cytoplasmic domains. Here, we review how talin-integrin and kindlin-integrin interactions, in cooperation with talin-lipid and kindlin-lipid interactions, regulate integrin affinities and how the progress in these areas helps us understand integrin-related diseases.
关键词: signal transduction transmembrane domain nanodisc integrin talin kindling cell adhesion
Expression of integrin in hepatic fibrosis and intervention of resveratrol
Jianye WU, Chuanyong GUO, Jun LIU, Xuanfu XUAN
《医学前沿(英文)》 2009年 第3卷 第1期 页码 100-107 doi: 10.1007/s11684-009-0013-x
关键词: liver fibrosis integrin-β1 resveratrol tumor growth factor-β tissue inhibitor of metalloproteinase-1
Coronary leukocyte activation in relation to progression of coronary artery disease
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《医学前沿(英文)》 2016年 第10卷 第1期 页码 85-90 doi: 10.1007/s11684-016-0435-1
Leukocyte activation has been linked to atherogenesis, but there is little in vivo evidence for its role in the progression of atherosclerosis. We evaluated the predictive value for progression of coronary artery disease (CAD) of leukocyte activation markers in the coronary circulation. Monocyte and neutrophil CD11b, neutrophil CD66b expression and intracellular neutrophil myeloperoxidase (MPO) in the coronary arteries were determined by flow cytometry in patients undergoing coronary angiography. The primary outcome included fatal and nonfatal myocardial infarction or arterial vascular intervention due to unstable angina pectoris. In total 99 subjects who were included, 70 had CAD at inclusion (26 patients had single-vessel disease, 18 patients had two-vessel disease and 26 patients had three-vessel disease). The median follow-up duration was 2242 days (interquartile range: 2142–2358). During follow-up, 13 patients (13%) developed progression of CAD. Monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO measured in blood obtained from the coronary arteries were not associated with the progression of CAD. These data indicate that coronary monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO do not predict the risk of progression of CAD.
关键词: coronary artery disease inflammation integrin myeloperoxidase leukocyte activation
外泌体CD44与整合素α6β4结合激活宿主细胞重塑肿瘤微环境促进胰腺癌恶性转移 Article
牟为, 许亚婕, 顾鹏飞, 王文斌, 李井泉, 葛阳, 王慧
《工程(英文)》 2021年 第7卷 第10期 页码 1415-1425 doi: 10.1016/j.eng.2020.08.013
绝大多数胰腺癌患者的死亡都是由于癌细胞迅速转移到肺、肝、脑等重要器官造成的。其中,胰腺癌肝转移是胰腺癌患者死亡率高的原因之一。来自胰腺癌细胞的外泌体通常富含跨膜蛋白,用于支持肿瘤微环境的重编程和远处转移性病变的进展。我们的研究发现,由外泌体传递的跨膜糖蛋白CD44通过重编程肿瘤微环境,参与了胰腺癌的转移过程。CD44与整合素α6β4相互作用形成复合物,激活细胞内骨架蛋白及其信号通路,进而调控Src和Ras信号级联反应,促进肿瘤细胞的运动。值得注意的是,我们还证明了CD44-α6β4复合物可以通过外泌体的旁分泌作用传递到靶区。肝细胞选择性摄取具有高表达CD44的肿瘤外泌体,并通过刺激细胞因子、促炎因子和生长因子产生转移前生态位,最终支持肿瘤转移。我们的研究结果表明,外泌体CD44有可能作为胰腺癌临床诊断和治疗的生物标志物。
标题 作者 时间 类型 操作
Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition
null
期刊论文
Expression of integrin in hepatic fibrosis and intervention of resveratrol
Jianye WU, Chuanyong GUO, Jun LIU, Xuanfu XUAN
期刊论文