KLF13 overexpression protects sepsis‐induced myocardial injury and LPS‐induced inflammation and apoptosis
KLF13 overexpression protects sepsis‐induced myocardial injury and LPS‐induced inflammation and apoptosis
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DOI：
10.1111/iep.12459
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发表时间：
2022-12
影响因子：
3
通讯作者：
Ni Zeng;Zaijin Jian;Wenxin Zhu;Junmei Xu;Yongmei Fan;Feng-Gang Xiao
中科院分区：
文献类型：
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作者：
Ni Zeng;Zaijin Jian;Wenxin Zhu;Junmei Xu;Yongmei Fan;Feng-Gang Xiao
败血症仍然是一个世界性的公共卫生问题。本研究旨在探讨转录因子（TF）在脓毒症引起的心肌损伤中的作用和机制。首先，选择TF KLF13来探讨其在脓毒症引起的心肌损伤中的作用。建立盲肠结扎穿刺（CLP）诱导的脓毒症小鼠模型，并使用标准组织病理学方法对脓毒症小鼠进行检查。在脓毒症小鼠心脏中检测到 KLF13 表达，并且在脂多糖 (LPS) 诱导的细胞炎症模型中也观察到 KLF13 表达。为了进一步探索这一点，在两种模型中都检测了促凋亡 cleaved-caspase3/caspase3 和 Bax 水平以及抗凋亡 Bcl2 水平，此外，在脓毒症小鼠和 LPS 诱导的细胞中检测了炎症细胞因子（IL-1β、TNF-α、IL-8 和 MCP-1）的产生、IκB-α 蛋白水平和 p65 磷酸化。因此，在相似的条件下评估了三个参数——心肌细胞凋亡、炎症反应和 NF-κB 通路激活。脓毒症小鼠水肿明显，肌丝排列紊乱，心肌细胞不同程度降解坏死。 KLF13 在脓毒症小鼠心脏和 LPS 诱导的细胞炎症模型中均下调。此外，两种模型均显示心肌细胞凋亡异常增加（cleaved-caspase3/caspase 和 Bax 蛋白水平增加，Bcl2 水平降低）、炎症升高（炎症细胞因子的产生增加）和 NF-κB 通路激活（p65 磷酸化增加和 IκB-α 蛋白水平降低）。 KLF13 过表达可显着改善体内和体外脓毒症引起的心肌损伤。 KLF13 过表达通过抑制炎症途径（特别是 NF-κB 信号传导）和心肌细胞凋亡，防止脓毒症诱导的心肌损伤和 LPS 诱导的细胞炎症和细胞凋亡。
Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis‐induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis‐induced myocardial injury. The caecal ligation and puncture (CLP) ‐induced sepsis mouse model was established and the septic mice were examined using standard histopathological methods. KLF13 expression was detected in the septic mouse heart and was also seen in a lipoploysaccharide (LPS) ‐induced cellular inflammation model. To explore this further both pro‐apoptotic cleaved‐caspase3/caspase3 and Bax levels and anti‐apoptotic Bcl2 levels were examined, also in both models, In addition inflammatory cytokine (IL‐1β, TNF‐α, IL‐8 and MCP‐1) production and IκB‐α protein level and p65 phosphorylation were examined in both septic mice and LPS‐induced cells. Thus three parameters ‐ cardiomyocyte apoptosis, inflammatory response and NF‐κB pathway activation were evaluated under similar conditions. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in the myocardial cells. KLF13 was downregulated in both the septic mouse heart and the LPS‐induced cellular inflammation model. Furthermore, both models showed abnormally increased cardiomyocyte apoptosis (increased cleaved‐caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF‐κB pathway (increased p65 phosphorylation and decreased IκB‐α protein level). KLF13 overexpression notably ameliorated sepsis‐induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis‐induced myocardial injury and LPS‐induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially NF‐κB signalling) and cardiomyocyte apoptosis.