Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Xueyuan Long, Yanpeng Yang, Ke Zhou
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Abstract

Background Sepsis triggers myocardial injury and dysfunction, leading to a high mortality rate in patients. Cardiomyocyte apoptosis plays a positive regulatory role in septic myocardial injury and dysfunction. However, the mechanism is unclear. Methods Bioinformatics analysis was used to identify differentially expressed genes in septic mice heart and validate key genes and pathways. The correlation of protein–protein and protein–pathway was analyzed. Sequentially, the cecal ligament and puncture (CLP) was used to induce septic mice, followed by Serpine1 inhibitor treatment. Finally, the regulatory relationship of Yes-associated protein1 (YAP1), Serpine1, and caspase-3 was verified in LPS-exposed mouse cardiomyocytes. Results Bioinformatic analysis found that Serpine1 expression is decreased in septic mice heart tissue and closely related to the HIPPO signaling pathway, while YAP1 is negatively correlated with apoptosis. In vivo, CLP induced a reduction of survival rate, cardiac dysfunction, and an increase in Serpine1 and Cleaved Caspase-3 expression, which could be reversed by a Serpine1 inhibitor. In vitro, LPS induced the mouse cardiomyocytes apoptosis, which could be reversed by Serpine1 inhibitor. Silencing YAP1 and Serpine1 reversed the LPS-induced increase in Serpine1 and Cleaved Caspase-3 expression, but silencing Serpine1 did not affect the LPS-induced YAP1 expression. Conclusion Sepsis induced mouse cardiomyocytes apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway.
败血症通过激活 YAP1/Serpine1/caspase-3通路诱导心肌细胞凋亡和心脏功能障碍
背景败血症会引发心肌损伤和功能障碍,导致患者的高死亡率。心肌细胞凋亡在脓毒症心肌损伤和功能障碍中起着积极的调节作用。然而,其机制尚不清楚。方法 采用生物信息学分析鉴定脓毒症小鼠心脏的差异表达基因,并验证关键基因和通路。分析了蛋白质与蛋白质、蛋白质与通路之间的相关性。依次用盲肠韧带和穿刺(CLP)诱导败血症小鼠,然后用 Serpine1 抑制剂治疗。最后,在暴露于 LPS 的小鼠心肌细胞中验证了 Yes-associated protein1(YAP1)、Serpine1 和 caspase-3 的调控关系。结果 生物信息学分析发现,Serpine1 在败血症小鼠心脏组织中表达减少,与 HIPPO 信号通路密切相关,而 YAP1 与细胞凋亡呈负相关。在体内,CLP诱导存活率下降、心脏功能障碍、Serpine1和裂解Caspase-3表达增加,而Serpine1抑制剂可逆转这些现象。在体外,LPS诱导小鼠心肌细胞凋亡,Serpine1抑制剂可逆转这一现象。沉默 YAP1 和 Serpine1 逆转了 LPS 诱导的 Serpine1 和裂解 Caspase-3 表达的增加,但沉默 Serpine1 并不影响 LPS 诱导的 YAP1 表达。结论 败血症通过激活 YAP1/Serpine1/caspase-3 通路诱导小鼠心肌细胞凋亡和心功能不全。
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来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
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