Identification of Key Molecular Signaling Pathways and Therapeutic Targets in Sepsis Shock

作者全名："Wang, Ke; Zhao, Ying; Zhang, Yongming; Tian, Jun; Li, Chenwei"

作者地址："[Wang, Ke; Zhao, Ying; Zhang, Yongming; Tian, Jun] Chongqing Med Univ, Yongchuan Hosp, Dept Clin Lab, Chongqing 402160, Peoples R China; [Li, Chenwei] Yubei Dist Peoples Hosp, Chongqing 401120, Peoples R China"

通信作者："Wang, K (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Dept Clin Lab, Chongqing 402160, Peoples R China."

来源：INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001165521900024

JCR分区：Q4

影响因子：0.5

年份：2023

卷号：85

期号：6

开始页：1677

结束页：1684

文献类型：Article

关键词：Sepsis; differentially expressed genes; protein-protein interaction; T-cell depletion; mortality

摘要："Sepsis shock was associated with worse mortality than common sepsis caused by disseminated infection. The present study had shown that repression of adaptive immunity was a characteristic of sepsis shock rather than sepsis, but the mechanism in which it exerted the adverse reaction was still need to be studied. In this study, we first employed weighted gene co-expression network analysis for acquiring the key modules with sepsis shock. Then, the differentially expressed genes and transcription factors were screened in the module for further function analysis, protein-protein interaction network building and long noncoding ribonucleic acid-micro ribonucleic acid-transcription factor network study. The study strengthened the concept that adaptive immune repression typically featured the sepsis shock concerning antigen presentation via major histocompatibility complex class II, T-cell activation and T-cell depletion. Among which T-cell depletion ranked as an overwhelming contributor to sepsis shock outcome. The transcription factor tumor protein P53, forkhead box protein O1 and GATA binding protein 3 served as the master regulator for the T-cell depletion process mainly through driving hematopoietic stem cells out of quiescence to unrestrained hematopoietic stem cell expansion with detrimental deoxyribonucleic acid damage, which greatly decreased hematopoietic stem cells long-term differentiation potential into T lymphocyte hierarchy. The study enlightened that manipulating the expression level of tumor protein P53, forkhead box protein O1 and GATA binding protein 3 to an optimized state will guarantee the T cell replenishment for fighting sepsis shock, which might support a potential efficient therapeutic way for sepsis shock treatment."

基金机构：Chongqing Natural Science Foundation [cstc-2019jcyj-msxmX0371]; Chongqing Science and Technology Commission [2020FYYX124]; Chongqing Health and the Health Committee

基金资助正文："This study was supported by Chongqing Natural Science Foundation (Grant No. cstc-2019jcyj-msxmX0371), Chongqing Health and the Health Committee and Chongqing Science and Technology Commission (Grant No. 2020FYYX124)."