LncRNA GAS5 downregulates NLRP3 inflammasome activation-mediated pyroptosis in sepsis-induced myocardial injury by targeting SIRT3/AMPKα

作者全名:"Luo, Minghao; Peng, Yuce; Lv, Dingyi; Xue, Yuzhou; Huang, Longxiang; Hu, Yu; Zhu, Wenyan; Luo, Suxin; Shen, Jian; Li, Xiang"

作者地址:"[Luo, Minghao; Peng, Yuce; Lv, Dingyi; Xue, Yuzhou; Huang, Longxiang; Hu, Yu; Luo, Suxin; Shen, Jian; Li, Xiang] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing 400016, Peoples R China; [Luo, Minghao; Peng, Yuce; Lv, Dingyi; Hu, Yu] Chongqing Med Univ, Cardiovasc Dis Lab, Chongqing 400016, Peoples R China; [Zhu, Wenyan] Chongqing Med & Pharmaceut Coll, Chongqing Engn Res Ctr Pharmaceut Sci, Chongqing 401331, Peoples R China; [Luo, Suxin] Chongqing Med Univ, Med Data Res Inst, Chongqing 400016, Peoples R China; [Shen, Jian; Li, Xiang] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者:"Shen, J; Li, X (通讯作者),Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing 400016, Peoples R China.; Shen, J; Li, X (通讯作者),Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源:HELIYON

ESI学科分类: 

WOS号:WOS:001132344700001

JCR分区:Q1

影响因子:3.4

年份:2023

卷号:9

期号:12

开始页: 

结束页: 

文献类型:Article; Early Access

关键词:Sepsis; GAS5; Myocardial injury; Pyroptosis

摘要:"An increasing body of studies has demonstrated the significance of long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) in inflammation and myocardial injury in septic shock. This research aims to determine whether GAS5 contributes to the pathological development of sepsis-induced cardiac damage and NLRP3 inflammasome-mediated myocardial cell pyroptosis. Cecal ligation and puncture (CLP) surgery was used to cause septic shock in C57BL/6 wild-type mice. After CLP, inflammatory, pyroptosis parameters of myocardial tissue, survival rate, and Murine Sepsis Score (MSS) were assessed to evaluate the involvement of GAS5 in the mouse myocardial depression. To investigate GAS5's function in lipopolysaccharide (LPS) induced myocardial cell pyroptosis, gain- and loss-of-function experiments were conducted in vitro on HL1 cells. Our findings indicated that CLP dramatically reduced survival rates, MSS, SIRT3 and pAMPK expression, and activated the Nuclear factor-kappa B (NF-kappa B) pathway and NLRP3 inflammasome-mediated pyroptosis. The NF-kappa B and pyroptosis pathways were greatly elevated while SIRT3/p-AMPK alpha was dramatically decreased as a result of GAS5 being downregulated. Meanwhile, the regulatory effect could be suppressed by SIRT3 and AMPK alpha activator. Our observations supported the idea that GAS5 has a crucial protective impact against myocardial inflammation and pyroptosis in sepsis."

基金机构:General Project of Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0221]; Intelligent Medicine Training Program of Chongqing Medical University [ZHYX202017]

基金资助正文:"<B>Funding</B> This work was supported by General Project of Chongqing Natural Science Foundation (Project number: cstc2020jcyj-msxmX1091) , General Project of Chongqing Natural Science Foundation (Project number: cstc2021jcyj-msxmX0221) , and Intelligent Medicine Training Program of Chongqing Medical University (Project number: ZHYX202017) ."