Transcriptome analysis reveals the mechanism of pyroptosis-related genes in septic cardiomyopathy

Haoyan Zhu; Jiahe Wu; Chenze Li; Ziyue Zeng; Tianwen He; Xin Liu; Qiongxin Wang; Xiaorong Hu; Zhibing Lu; Huanhuan Cai

doi:10.7717/peerj.16214

Transcriptome analysis reveals the mechanism of pyroptosis-related genes in septic cardiomyopathy

PeerJ. 2023 Oct 19:11:e16214. doi: 10.7717/peerj.16214. eCollection 2023.

Authors

Haoyan Zhu^#^{1

2}, Jiahe Wu^#^{1

2}, Chenze Li^{1

2}, Ziyue Zeng^{1

2}, Tianwen He^{1

2}, Xin Liu^{1

2}, Qiongxin Wang^{1

2}, Xiaorong Hu^{1

2}, Zhibing Lu^{1

2}, Huanhuan Cai^{1

2}

Affiliations

¹ Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.

^# Contributed equally.

Abstract

Background: Septic cardiomyopathy (SC) is characterized by myocardial dysfunction caused by sepsis and constitutes one of the serious complications of sepsis. Pyroptosis is a unique proinflammatory programmed cell death process. However, the role of pyroptosis in the development of SC remains unclear, and further study is required. The purpose of this study is to identify pyroptosis-related genes (PRGs) in SC and explore the mechanism of pyroptosis involved in the regulation of SC formation and progression.

Methods: Differential expression analysis and enrichment analysis were performed on the SC-related dataset GSE79962 to identify differentially expressed genes (DEGs). PRGs were screened by intersecting genes associated with pyroptosis in previous studies with the DEGs obtained from GSE79962. The expression pattern of them was studied based on their raw expression data. Additionally, corresponding online databases were used to predict miRNAs, transcription factors (TFs) and therapeutic agents of PRGs. Lipopolysaccharide (LPS)-induced cell damage models in H9C2 and AC16 cell lines were constructed, cell activity was detected by CCK-8 and cell pyroptosis were detected by Hoechst33342/PI staining. Furthermore, these PRGs were verified in the external datasets (GSE53007 and GSE142615) and LPS-induced cell damage model. Finally, the effect of siRNA-mediated PRGs knockdown on the pyroptosis phenotype was examined.

Results: A total of 1,206 DEGs were screened, consisting of 663 high-expressed genes and 543 low-expressed genes. Among them, ten PRGs (SOD2, GJA1, TIMP3, TAP1, TIMP1, NOD1, TP53, CPTP, CASP1 and SAT1) were identified, and they were mainly enriched in "Pyroptosis", "Ferroptosis", "Longevity regulating pathway", and "NOD-like receptor signaling pathway". A total of 147 miRNAs, 31 TFs and 13 therapeutic drugs were predicted targeting the PRGs. The expression trends of SOD2 were confirmed in both the external datasets and LPS-induced cell damage models. Knockdown of SOD2 induced increased pyroptosis in the AC16 LPS-induced cell damage model.

Conclusions: In this study, we demonstrated that SOD2 is highly expressed in both the SC and LPS-induced cell damage models. Knockdown of SOD2 led to a significant increase in pyroptosis in the AC16 LPS-induced cell damage model. These findings suggest that SOD2 may serve as a potential target for the diagnosis and treatment of SC.

Keywords: Bioinformatics analysis; Biomarker; Immune Infiltration; Pyroptosis; Septic Cardiomyopathy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiomyopathies* / genetics
Gene Expression Profiling
Humans
Lipopolysaccharides
MicroRNAs*
Pyroptosis
Sepsis*

Substances

Lipopolysaccharides
MicroRNAs

Grants and funding

This study was supported by a grant from the National Natural Science Foundation of China (No. 82070425, Zhibing Lu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.