hnRNP K通过c-IAP2 mRNA抑制脓毒症巨噬细胞凋亡的信号机制研究

批准号:
82002089
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
李磊
依托单位:
学科分类:
脓毒症
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
李磊
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中文摘要
巨噬细胞凋亡是脓毒症发生发展的重要病理生理基础,探讨其调控机制具有重要意义。研究报道核不均一核糖核蛋白K(hnRNP K)对细胞凋亡具有重要调控作用。我们前期发现:在炎症反应中hnRNP K蛋白与凋亡抑制因子2(c-IAP2)mRNA亲和力增强;敲低hnRNP K会降低c-IAP2基因表达,巨噬细胞凋亡增加;抑制细胞外调节蛋白激酶(ERK)通路导致hnRNP K磷酸化水平降低,c-IAP2 mRNA下降,同时伴随巨噬细胞凋亡上调。在此基础上我们提出假说:脓毒症中hnRNP K依赖ERK通路发生磷酸化修饰,进而上调c-IAP2 mRNA,抑制巨噬细胞凋亡,从而促进炎症的进展。本项目拟在细胞水平研究hnRNP K磷酸化对c-IAP2 mRNA的调控作用,探讨hnRNP K抑制脓毒症巨噬细胞凋亡的分子机制;并通过基因敲除探索hnRNP K对脓毒症小鼠的保护效应,以期为临床干预脓毒症提供新策略。
英文摘要
Macrophage apoptosis is an important pathophysiological basis for the development of sepsis, and the regulatory mechanism is of great significance. It has been reported that nuclear heterogeneous ribonucleoprotein K (hnRNP K) plays an important role in apoptosis. Our previous study showed that the affinity between hnRNP K and cellular inhibitor of apoptosis 2 (c-IAP2) mRNA was increased in inflammation. We observed that knockdown of hnRNP K would decrease the expression of c-IAP2 mRNA and promote macrophage apoptosis. Furthermore, the inhibition of the extracellular regulated protein kinase (ERK) pathway led to reduced level of hnRNP K phosphorylation, which contributed to decreasing c-IAP2 mRNA and promoting macrophage apoptosis. Based on the results, we propose that the phosphorylation of hnRNP K depends on the ERK pathway in sepsis, which increases the expression of c-IAP2 mRNA and inhibits macrophage apoptosis that promotes the progression of inflammation. The project will research into the regulation of hnRNP K phosphorylation on c-IAP2 mRNA expression at the cellular level, and explore the molecular mechanism of hnRNP K inhibiting macrophage apoptosis in sepsis. In addition, we explore the protection to septic mice by hnRNP K knockout mice. The study is to provide a new strategy for clinical intervention in sepsis.
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DOI:10.1186/s12953-023-00220-x
发表时间:2023-10-24
期刊:PROTEOME SCIENCE
影响因子:2
作者:Xu, Jia;Liu, Jiacheng;Qu, Yibai;Jiang, Linhui;Liang, Rongxin;Li, Bohai;Li, Lei;Jiang, Yong
通讯作者:Jiang, Yong
DOI:10.1016/j.jare.2021.11.005
发表时间:2022-07
期刊:JOURNAL OF ADVANCED RESEARCH
影响因子:10.7
作者:Li, Lei;Huang, Lin;Huang, Chenyang;Xu, Jia;Huang, Yukai;Luo, Haihua;Lu, Xinya;He, Shuyue;Yuan, Gang;Chen, Li;Han, Xue;Cao, Xusong;Jiang, Aolin;Liu, Cuiting;Shi, Junmin;Yang, Hong;Jiang, Yong
通讯作者:Jiang, Yong
脓毒症血小板外泌体通过20S蛋白酶体对急性肺损伤的保护作用及其机制研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:52万元
- 批准年份:2022
- 负责人:李磊
- 依托单位:
国内基金
海外基金
