2. Academic Validation
  3. DDX3X deficiency alleviates LPS-induced H9c2 cardiomyocytes pyroptosis by suppressing activation of NLRP3 inflammasome

DDX3X deficiency alleviates LPS-induced H9c2 cardiomyocytes pyroptosis by suppressing activation of NLRP3 inflammasome

  • Exp Ther Med. 2021 Dec;22(6):1389. doi: 10.3892/etm.2021.10825.
Dandan Feng 1,  Liang Guo 2,  Jing Liu 3,  Yunxuan Song 4,  Xiuyuan Ma 1,  Haiyang Hu 1,  Ju Liu 3,  Enkui Hao 1
Affiliations

Affiliations

  • 1 Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
  • 2 Department of Anesthesiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China.
  • 3 Laboratory of Microvascular Medicine, Medical Research Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China.
  • 4 Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong 250014, P.R. China.
PMID: 34650637 DOI: 10.3892/etm.2021.10825
Abstract

Increasing evidence suggest that NOD-like Receptor protein 3 (NLRP3) inflammasome-mediated Pyroptosis may be the underlying pathological mechanism of sepsis-induced cardiomyopathy. DDX3X, an ATP-dependent RNA helicase, plays a vital role in the formation of the NLRP3 inflammasome by directly interacting with cytoplasmic NLRP3. However, whether DDX3X has a direct impact on lipopolysaccharide (LPS)-induced cardiomyocyte injury by regulating NLRP3 inflammasome assembly remains unclear. The present study aimed to investigate the role of DDX3X in the activation of the NLRP3 inflammasome and determine the molecular mechanism of DDX3X action in LPS-induced Pyroptosis in H9c2 cardiomyocytes. H9c2 cardiomyocytes were treated with LPS to simulate sepsis in vitro. The results demonstrated that LPS stimulation upregulated DDX3X expression in H9c2 cardiomyocytes. Furthermore, Ddx3x knockdown significantly attenuated Pyroptosis and cell injury in LPS-treated H9c2 cells by suppressing NLRP3 inflammasome activation. Taken together, these results suggest that DDX3X is involved in LPS-induced cardiomyocyte Pyroptosis, and DDX3X deficiency mitigates cardiomyocyte damage induced by LPS treatment.

Keywords

DDX3X; NOD-like receptor protein 3 inflammasome; lipopolysaccharide-induced cardiomyocyte injury; pyroptosis; reactive oxygen species.

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