课题基金基金详情
丙酮酸激酶PKM2对中性粒细胞脱颗粒调控进而影响急性炎症的机制研究
结题报告
批准号:
32000634
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
孙鑫磊
依托单位:
学科分类:
感染与非感染性炎症
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
孙鑫磊
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中文摘要
中性粒细胞(PMN)在天然免疫防御过程中发挥着重要的作用,其中脱颗粒是PMN最主要的防御方式之一。然而,PMN释放不同颗粒的机制尚不完全明确。PMN脱颗粒涉及到突触体相关蛋白(SNAP)家族参与,研究表明与PMN代谢方式类似的肿瘤细胞中有氧糖酵解关键酶——丙酮酸激酶(PKM2)可以调控SNAP-23影响外泌体的释放,在PMN中PKM2调控SNAP家族蛋白脱颗粒机制仍未知。我们首次发现PMN在刺激下特异性颗粒和明胶颗粒的释放与有氧糖酵解正相关。此外,PKM2通过自身磷酸化而磷酸化SNAP-23,同时特异性敲除小鼠PMN在迁移等功能均被抑制。因此我们提出假说:PMN中PKM2通过调控SNAP-23选择性释放颗粒进而影响后续炎症反应。本研究旨在阐明PKM2调控PMN脱颗粒机制,并针对PKM2通过SNAP-23蛋白调节PMN脱颗粒探究其在炎症相关疾病发生发展机制,对相关疾病治疗具有重大的指导意义。
英文摘要
Neutrophil plays an important role in immune defense, and degranulation is one of the most important defense methods in neutrophil.However, the mechanism by which different particles are released from the neutrophil remain incompletely understood. Degranulation is mainly due to activation of intracellular signaling pathways, such as the granule-associated synaptosome-associated protein (SNAP). Previously studies have shown that pyruvate kinase, a key enzyme for aerobic glycolysis in tumor cells similar to neutrophil metabolism, can regulate the release of SNAP-23 from the exosomes, PKM2 regulates SNAP family proteins in neutrophil and thus release the different particles is unknown. We discovered recently that the release of specific granules and gelatin granules under the stimulation of neutrophil was closely related to the increase of aerobic glycolysis. Further studies have shown that inflammation stimulates neutrophil, and PKM2 can modulate SNAP-23 release by self-phosphorylation, which in turn affects the release of specific particles and gelatin particles, at the same time, neutrophil migration in neutrophil-specific PKM2 deficient mice was affected. Therefore, we hypothesize that PKM2 may modulate SNAP-23 to release specific granules and gelatin granules during neutrophil activation, without affecting the release of azurophil granules, thus affecting the related immune function.The purpose of this study is to elucidate the mechanism of PKM2 regulating neutrophil degranulation, and through the mechanism of regulating neutrophil degranulation by PKM2 through SNAP-23 to explore the development of inflammatory related diseases, which is of great significance for the treatment of inflammatory related diseases. 
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DOI:10.1111/jcmm.17900
发表时间:2023-11
期刊:JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
影响因子:5.3
作者:Shi, Fujie;Wu, Yunfei;Wang, Kai;Wang, Jiafan;Liu, Minghui;Sun, Xinlei
通讯作者:Sun, Xinlei
DOI:--
发表时间:2021
期刊:Cell Mol Immunol
影响因子:--
作者:Xinlei Sun;Dong Wang;Yan Wang;Lei Ye;Fujie Shi;Shuang Qu;Hongwei Liang;Ke Ze
通讯作者:Ke Ze
DOI:doi: 10.3390/biomedicines10051193doi: 10.3390/biomedicines10051193
发表时间:2022
期刊:Biomedicines
影响因子:4.7
作者:Xinlei Sun;Fujie Shi;Weiran Wang;Yunfei Wu;Shuang Qu;Jing Li;Hongwei Liang;Ke Zen
通讯作者:Ke Zen
国内基金
海外基金