受体介导胞内信号调控血小板活化和活性物质释放，是血小板参与多种生理病理过程的基础，研究血小板活化与释放的调控机制具有重要意义。五年来，申请人围绕血小板活化胞内调控机制和α-granule释放调控机制展开研究，发现PTEN能够通过PI3K/Akt信号通路依赖和非依赖途径调控血小板活化；发现PDK1/Akt/Gsk3β信号轴是血小板活化的关键调控通路；发现ADP受体P2Y12通过cAMP/PKA通路调控血小板α-granule释放炎症因子招募单核细胞加速动脉粥样硬化恶化；发现α-granule中新蛋白成分Angptl2通过PIRB受体抑制血小板活化是血小板活化自控的重要机制。这些系列研究成果连续发表在血液学权威期刊《Blood》等杂志上，得到国际上本领域著名专家的积极评述和广泛引证，展示了以血小板为靶的多种疾病的治疗潜力。本申请将继续围绕血小板活化和分泌的调控网络开展研究。

Platelets are involved in many pathophysiological processes. It is necessary to elucidate the mechanism underlying platelet activation and secretion. During the past five years, the applicant focused on investigation of molecular mechanisms of platelet activation and α-granules secretion, and found that PTEN regulated platelet activation and secretion via PI3K/Akt pathway-dependent and -independent manners. PDK1/Akt/Gsk3β signaling axis was an important factor in regulation of platelet activation. ADP receptor P2Y12-mediated cAMP/PKA pathway was revealed to aggravate atherosclerosis by enhancing the release of chemokines from platelet α-granule. Angiopoietin-Like Protein 2 (Angptl2) was identified for the first time in the platelet α-granules, and the inhibitory function of Angptl2 via its receptor PIRB was revealed as an important self-control mechanism of platelet activation. These findings were published on world-renowned journal BLOOD, which were highlighted and broadly cited. The applicant’s discoveries not only further enrich our understanding of the mechanisms in platelet activation and secretion, but also show the potential of platelet-targeted treatment of a variety of diseases. In this proposal, the applicant will continue elucidating the regulatory network underlying platelet activation and secretion.