Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation.
Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation.
复制标题
DOI：
10.3389/fcvm.2022.923066
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Lai, Song-Qing
中科院分区：
文献类型：
--
作者：
Zou, Hua-Xi;Qiu, Bai-Quan;Zhang, Ze-Yu;Hu, Tie;Wan, Li;Liu, Ji-Chun;Huang, Huang;Lai, Song-Qing
脓毒症心肌病（SCM）是脓毒症引起的严重器官功能障碍，预后不良，其病理生物学机制尚不清楚。自噬是最近关注 SCM 的一个生物学过程，但目前对自噬失调在 SCM 发病机制中的作用的理解仍然有限且不确定。基于人类病理样本的转录组探索疾病的分子机制可能会带来最接近的见解。在本研究中，我们基于人类脓毒症心脏的转录组分析了SCM中自噬相关基因的差异表达，并进一步探讨了它们潜在的串扰和功能通路。通过构建蛋白质-蛋白质相互作用网络来鉴定关键功能模块和枢纽基因。在脂多糖（LPS）诱导的 H9c2 心肌细胞损伤模型中进行验证后，确定了调节 SCM 自噬的 8 个关键基因（CCL2、MYC、TP53、SOD2、HIF1A、CTNNB1、CAT 和 ADIPOQ）以及自噬特征。此外，我们发现关键基因与脓毒症心脏中的异常免疫浸润有关，并且有可能作为生物标志物。最后，我们根据我们的结果预测了可能通过调节自噬在 SCM 中发挥保护作用的药物。我们的研究基于人类脓毒症心脏转录组为自噬在SCM中的作用提供了证据和新的见解，这对于揭示SCM的分子病理机制和探索SCM的诊断和治疗靶点具有重要意义。
Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein–protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM.
登录
查看更多内容
DOI：
10.1186/s13054-018-2043-8
发表时间：
2018-05-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
Ehrman RR;Sullivan AN;Favot MJ;Sherwin RL;Reynolds CA;Abidov A;Levy PD
通讯作者：
Levy PD
DOI：
10.1097/shk.0000000000000520
发表时间：
2016-04
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Araújo CV;Campbell C;Gonçalves-de-Albuquerque CF;Molinaro R;Cody MJ;Yost CC;Bozza PT;Zimmerman GA;Weyrich AS;Castro-Faria-Neto HC;Silva AR
通讯作者：
Silva AR
影响因子：
11.4
作者：
Coliva, Giulia;Duarte, Sofia;Fedorova, Maria
通讯作者：
Fedorova, Maria
DOI：
10.1007/978-981-15-0602-4_27
发表时间：
2019-01-01
期刊：
AUTOPHAGY: BIOLOGY AND DISEASES: BASIC SCIENCE
影响因子：
--
作者：
Cui, Bing;Lin, Heng;Hu, Zhuowei
通讯作者：
Hu, Zhuowei
影响因子：
19
作者：
Balaburski GM;Hontz RD;Murphy ME
通讯作者：
Murphy ME