最新出版的著名血液学专业杂志《血液》(Blood)，刊出了我国科学家的研究成果。该成果对止血及血栓形成的分子机制进行了分析和研究，首次发现血小板中一些物质的相互作用可能是一种安全有效防治血栓性疾病的新途径。该项研究由上海血液学研究所研究员、医学基因组学国家重点实验室血栓与止血课题组长奚晓东教授主持完成。
经过3年半研究，奚晓东教授和他的课题组认为一种名叫“整合素β3”细胞粘附分子是血栓形成的关键“控制点”，如果能对它及其相关信号的转导通路进行有效控制，就将有助于防治血栓性疾病。
原始出处：
Blood，1 August 2008, Vol. 112, No. 3, pp. 592-602，Xiaoyu Su, Xiaodong Xi
RGT, a synthetic peptide corresponding to the integrin β3 cytoplasmic C-terminal sequence, selectively inhibits outside-in signaling in human platelets by disrupting the interaction of integrin IIbβ3 with Src kinase
Xiaoyu Su1,2,*, Jianqing Mi2,3,*, Jinsong Yan1,2, Panagiotis Flevaris4, Yuanjing Lu1,2, Hongchen Liu1,2, Zheng Ruan1,2, Xuefeng Wang1,2, Nelly Kieffer5, Saijuan Chen1,2, Xiaoping Du4, and Xiaodong Xi1,2,5
1 State Key Laboratory of Medical Genomics, 2 Shanghai Institute of Hematology, 3 Department of Hematology, all at Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 4 Department of Pharmacology, University of Illinois at Chicago; and 5 Centre National de la Recherche Scientifique LIA 142, Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Mutational analysis has established that the cytoplasmic tail of the integrin β3 subunit binds c-Src (termed as Src in this study) and is critical for bidirectional integrin signaling. Here we show in washed human platelets that a cell-permeable, myristoylated RGT peptide (myr-RGT) corresponding to the integrin β3 C-terminal sequence dose-dependently inhibited stable platelet adhesion and spreading on immobilized fibrinogen, and fibrin clot retraction as well. Myr-RGT also inhibited the aggregation-dependent platelet secretion and secretion-dependent second wave of platelet aggregation induced by adenosine diphosphate, ristocetin, or thrombin. Thus, myr-RGT inhibited integrin outside-in signaling. In contrast, myr-RGT had no inhibitory effect on adenosine diphosphate-induced soluble fibrinogen binding to platelets that is dependent on integrin inside-out signaling. Furthermore, the RGT peptide induced dissociation of Src from integrin β3 and dose-dependently inhibited the purified recombinant β3 cytoplasmic domain binding to Src-SH3. In addition, phosphorylation of the β3 cytoplasmic tyrosines, Y747 and Y759, was inhibited by myr-RGT. These data indicate an important role for β3-Src interaction in outside-in signaling. Thus, in intact human platelets, disruption of the association of Src with β3 and selective blockade of integrin IIbβ3 outside-in signaling by myr-RGT suggest a potential new antithrombotic strategy.
