Data from: High-throughput mRNA sequencing-based DEGs: HNF4A mitigates sepsis-associated lung injury by upregulating NCOR2/GR/STAB1 axis and promoting macrophage polarization towards M2 phenotype
Data files
Feb 18, 2025 version files 265.25 KB
Abstract
Sepsis can trigger systemic inflammation and lead to detrimental effects on several organs, with particular emphasis on the lungs. In sepsis-associated lung injury, macrophages assume a pivotal role, as their overactivation could facilitate the secretion of inflammatory factors and the imbalance of polarization. Hepatocyte nuclear factor 4 alpha (HNF4A) has been reported its potential involvement in the regulation of inflammatory response and macrophage polarization. This study discusses the role and mechanism of HNF4A in sepsis-induced lung damage. HNF4A exhibits a decrease in expression by analyzing the differentially expressed genes in the lungs of septic mice from the Gene Expression Omnibus dataset GSE15379. Then, we established a mouse sepsis model through a cecal ligation and puncture method, and observed that the expression of HNF4A was reduced in both lung tissues and alveolar macrophages. To evaluate the function of HNF4A, we overexpressed HNF4A mediated by adenovirus vectors, which were injected into mice. We found that HNF4A overexpression resulted in a higher survival rate in septic mice and an amelioration of pulmonary damage. Meanwhile, HNF4A overexpression mitigated the infiltration of inflammatory cells and impeded the M1 polarization but facilitated the M2 polarization of macrophages in the lung tissues or the alveolar lavage fluid. In vitro, we treated bone marrow-derived macrophages with interleukin-4. Consistent results were obtained that HNF4A overexpression promoted the M2 polarization of macrophages. Mechanistically, we found that HNF4A transcriptionally regulate the expression of nuclear receptor coactivator 2 (NCOA2) through binding to its promoter region. NCOA2 interacted with glucocorticoid receptor (GR). Stabilin 1 (STAB1) was selected as a possible target by transcriptome sequencing analysis. Functional experiments confirmed STAB1 as a downstream target of the HNF4A/NCOA2/GR axis. Overall, this research investigated the potential impact of HNF4A on pulmonary injury in sepsis. It is suggested that one of the regulatory mechanisms involved in this association may be the NCOR2/GR/STAB1 axis.
Introduction
This dataset includes information on high-throughput mRNA sequencing-based DEGs in the article “HNF4A mitigates sepsis-associated lung injury by upregulating NCOR2/GR/STAB1 axis and promoting macrophage polarization towards M2 phenotype”.
File list
IL-4 + Ad-HNF4A + Dex + Ad-shNCOA2_vs_shNCIL-4 + Ad-HNF4A + Dex + Ad-shNCOA2.Differentially_Expressed_Genes, in xlsx format.
Author Information
Name: Yu-Hang Yang
Institution: Shengjing Hospital of China Medical University, Shenyang, China
Co-investigator 1
Name: Ri Wen
Institution: Shengjing Hospital of China Medical University, Shenyang, China
Co-investigator 2
Name: Xin-Mei Huang
Institution: Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
Co-investigator 3
Name: Tao Zhang
Institution: Shengjing Hospital of China Medical University, Shenyang, China
Co-investigator 4
Name: Ni Yang
Institution: Shengjing Hospital of China Medical University, Shenyang, China
Co-investigator 5
Name: Chun-Feng Liu
Institution: Shengjing Hospital of China Medical University, Shenyang, China
Corresponding author
Name: Dr. Tie-Ning Zhang
Institution: Shengjing Hospital of China Medical University, Shenyang, China
Description of the data and file structure
The variables of the data file includes: ESEMBL id (https://asia.ensembl.org/index.html) of the genes followed by the gene symbol, description of the gene, gene expression expressed in log2fold change. The data presented in this dataset provides information of the high-throughput mRNA sequencing-based DEGs in article “HNF4A mitigates sepsis-associated lung injury by upregulating NCOR2/GR/STAB1 axis and promoting macrophage polarization towards M2 phenotype”. Briefly, Bone marrow-derived macrophages (BMDMs) were cultured in the medium containing Ad-NC or Ad-HNF4A for 48h. Cells were treated with IL-4 for 24 h to induce M2 polarization. The 100 nM dexamethasone (Dex) was added to activate the GR pathway. shNCOA2 and shGR were synthesized to knock down the expression of NCOA2 and GR by adenovirus delivery to infected macrophages. Total RNA was extracted from cells using Trizol. mRNA was subsequently purified from the total RNA utilizing poly-T oligo-attached magnetic beads. Sequencing libraries were constructed employing the NEBNext Ultra RNA Library Prep Kit for Illumina, in accordance with the manufacturer's recommendations. The original fluorescence image files obtained from the Illumina platform were converted into short reads through base calling, and these short reads were recorded in FASTQ format. Fastp was utilized to conduct basic statistical analysis on the quality of the raw reads. The differentially expressed genes (DEGs) were screened as log2FC > 1 or log2FC < -1, and adj.p < 0.05.The column heading “symbol” indicates the name of DEGs. Missing data mentioned as n/a.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (82102254 to Tie-Ning Zhang, and 81971810 to Chun-Feng Liu), Liaoning Province Science and Technology Major Special Project (No.2020JH1/10300001 to Chun-Feng Liu), and 345 Talent Program of Shengjing Hospital of China Medical University (M1308 to Tie-Ning Zhang and M1404 to Ni Yang).