Regulation of Alternative Splicing of Lipid Metabolism Genes in Sepsis-Induced Liver Damage by RNA-Binding Proteins.

Autor: Abuduaini B; Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, 393 South Li Yu Shan Road, Ürümqi, 830054, Xinjiang, China., Jiyuan Z; First Clinical institute of Xinjiang Medical University, Ürümqi, 830054, Xinjiang, China., Rehati A; Department of Gastroenternology, The First Affiliated Hospital of Xinjiang Medical University, 393 South Li Yu Shan Road, Ürümqi, 830054, Xinjiang, China., Liang Z; Department of General Surgery, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830054, Xinjiang, China., Yunlin S; Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, 393 South Li Yu Shan Road, Ürümqi, 830054, Xinjiang, China. 1f7024syl@xjmu.edu.cn.; Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University,State Key Laboratory of Pathogenesis, Prevention and Treatment of high Incidence Diseases in Central Asia, 393 South Li Yu Shan Road, Ürümqi, 830054, Xinjiang, China. 1f7024syl@xjmu.edu.cn.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2024 Dec; Vol. 47 (6), pp. 1952-1968. Date of Electronic Publication: 2024 May 09.
DOI: 10.1007/s10753-024-02017-2
Abstrakt: RNA binding proteins (RBPs) have the potential for transcriptional regulation in sepsis-induced liver injury, but precise functions remain unclear. Our aim is to conduct a genome-wide expression analysis of RBPs and illuminate changes in the regulation of alternative splicing in sepsis-induced liver injury. RNA-seq data on "sepsis and liver" from the publicly available NCBI data set was analyzed, and differentially expressed RBPs and alternative splicing events (ASEs) in the healthy and septic liver were identified. Co-expression analyses of sepsis-regulated RBPs and ASEs were performed. Models of sepsis were established to validate hepatic RBP gene expression patterns with different treatments. Pairwise analysis of gene expression profiles of sham, cecum ligation puncture (CLP), and CLP with dichloroacetate (CLPDCA) mice allowed 1208 differentially expressed genes (DEGs), of which 800 were up-regulated and 408 down-regulated, to be identified. DEGs were similar in both Sham and CLPDCA mice. The KEGG analysis showed that up-regulated genes as being involved in cytokine-cytokine receptor interaction and IL-17 signaling pathway and down-regulated genes in metabolic pathways. Differences in lipid metabolism-related alternative splicing events, including A3SS, were also found in CLP and CLPDCA compared with sham mice. Thirty-seven RBPs, including S100a11, Ads2, Fndc3b, Fn1, Ddx28, Car2, Cisd1, and Ptms, were differentially expressed in CLP mice and the regulated alternative splicing genes(RASG) with the RBP shown to be enriched in lipid metabolic and oxidation-reduction-related processes by GO functional analysis. In KEEG analysis the RASG mainly enriched in metabolic pathway. The models of sepsis were constructed with different treatment groups, and S100a11 expression in the CLP group found to be higher than in the sham group, a change that was reversed by DCA. The alternative splicing ratio of Srebf1 and Cers2 decreased compared with the sham group increased after DCA treatment. Abnormal profiles of gene expression and alternative splicing were associated with sepsis-induced liver injury. Unusual expression of RBPs, such as S100a11, may regulate alternative splicing of lipid metabolism-associated genes, such as Srebf1 and Cers2, in the septic liver. RBPs may constitute potential treatment targets for sepsis-induced liver injury.
Competing Interests: DECLARATIONS. Ethical Approval: The study proposal was submitted to the Health Research and Ethics Committee of the first affiliated hospital of Xinjiang Medical University for review. The committee exempted the proposal and provided a letter of exemption from review (Approval Number:K202309-29). Consent for Publication: Not applicable Competing Interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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