PMID- 32958127 OWN - NLM STAT- MEDLINE DCOM- 20201110 LR - 20201110 IS - 1007-8738 (Print) IS - 1007-8738 (Linking) VI - 36 IP - 8 DP - 2020 Aug TI - [Bioinformatic analysis of Eftud2 enhancing mouse macrophage function]. PG - 704-711 AB - Objective To elucidate the mechanisms by which elongation factor Tu GTP binding domain containing 2 (Eftud2) enhances the immune function of murine macrophages by bioinformatics analysis. Methods The bone marrow-derived macrophages (BMDMs) of Eftud2 myeloid cell-specific knockout (MKO) mice (n=10) and wild-type (WT) littermates (n=10) were collected and stimulated by lipopolysaccharide (LPS) (100 ng/mL) for 2 hours. Bioinformatics analysis was conducted to examine the differences in gene expression and mRNA transcription levels. The the differences in gene expression and alternative splicing of mRNA transcription in BMDMs were analyzed by DEGseq and rMATS, respectively. The signaling pathways affected were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) classification and enrichment methods. Results Compared with WT counterparts, the expression levels of IL-6, IL-1beta, TNF-alpha, and the genes related to immune response in MKO BMDMs were down-regulated following LPS stimulation. KEGG pathway analysis showed that the differently expressed genes in BMDMs and alternative splicing mainly affected the signal transduction and immune system-related metabolic pathways, and had a strong correlation with PI3K-AKT signaling pathway. The difference in alternative splicing also existed in ubiquitination and endocytosis. Compared with WT counterparts, there were 232 differences in alternative splicing in MKO BMDMs, among which 125 were skipping exons, accounting for the largest proportion. In addition, the analysis of alternative splicing differences also confirmed the previous experimental results, that is, Eftud2 could participate in the activation of inflammatory signaling pathways by enhancing the alternative splicing of key molecules such as MyD88 in TLR4-NF-kappaB signaling pathway, thereby augmenting the function of macrophages. Conclusion Eftud2 can promote the release of inflammatory cytokines in BMDMs by regulating gene expression and alternative splicing, and consequently enhance the immune function of macrophages. FAU - Sun, Ying AU - Sun Y AD - Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010058; Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China. FAU - Yang, Peng AU - Yang P AD - Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010058; Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China. FAU - Lyu, Zhonglin AU - Lyu Z AD - Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850; Department of Hematology, Second Medical Center, PLA General Hospital, Beijing 100039, China. FAU - Zheng, Yuanqiang AU - Zheng Y AD - Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010058, China. FAU - Shi, Yanchun AU - Shi Y AD - Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010058, China. *Corresponding authors, E-mail: ycshi5388@163.com. FAU - Chen, Guojiang AU - Chen G AD - Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China. *Corresponding authors, E-mail: jyk62033@163.com. LA - chi PT - Journal Article PL - China TA - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi JT - Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology JID - 101139110 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) SB - IM MH - Animals MH - *Computational Biology MH - Cytokines/genetics/immunology MH - *Gene Expression/genetics/immunology MH - Lipopolysaccharides/pharmacology MH - *Macrophages/immunology MH - Mice MH - NF-kappa B/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism EDAT- 2020/09/23 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/09/22 05:31 PHST- 2020/09/22 05:31 [entrez] PHST- 2020/09/23 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PST - ppublish SO - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2020 Aug;36(8):704-711.