HuR promotes miRNA-mediated upregulation of NFI-A protein expression in MDSCs during murine sepsis

Bah, Isatou; Alkhateeb, Tuqa; Kumbhare, Ajinkya; Youssef, Dima; Yao, Zhi Q.; Hawkin, Gregory A.; McCall, Charles E.; Gazzar, Mohamed El

doi:10.1016/j.molimm.2020.04.014

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…For instance, miR-23a improved sepsis lung injury through PI3K/Akt/ p 53 pathway [ 8 ]. MiR-21 and miR-181b targeted NFI-A to enhance resistance to sepsis infection [ 9 ]. Overexpression of miR-21 had a protective effect on sepsis-induced renal cell apoptosis through PTEN/PI3K/Akt signaling pathway [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders

Shen

Xie

Peng

et al. 2022

Computational Intelligence and Neuroscience

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Purpose. Present study is aimed to explore the role of miR-186-5p in sepsis-induced coagulation disorders and molecular mechanisms. Methods. Thirty-four sepsis patients and 34 respiratory infection/pneumonia patients were selected in the present study. Polymicrobial sepsis model was created by cecal ligation and puncture (CLP). The mRNA expression was detected by qRT-PCR. Western blot was utilized to measure protein expression. Thromborel S Reagent was applied to measure the prothrombin time (PT). Platelet count of blood was measured via LH 780. ELISA kits were utilized to evaluate the fibrinogen and PAI-1 concentration. Results. MiR-186-5p expression was lower and nicotinamide phosphoribosyltransferase (NAMPT) mRNA expression was higher in sepsis patients in contrast to control group. Coagulation time was markedly prolonged and platelet count was markedly decreased in CLP mice. In addition, fibrinogen concentration was obviously lower and PAI-1 concentration was obviously higher in CLP mice. MiR-186-5p mimic obviously decreased coagulation time and PAI-1 concentration, while raised platelet count and fibrinogen concentration. Targetscan predicted miR-186-5p might directly regulates NAMPT, and luciferase reporter assay verified this prediction. In addition, miR-186-5p mimic obviously inhibited the mRNA expression of NAMPT. Knockdown of NAMPT improved coagulation dysfunction in sepsis. Overexpression of NAMPT reversed the improvement effect of miR-186-5p on coagulation dysfunction. MiR-186-5p mimic markedly inhibited NF-κB pathway. Conclusion. MiR-186-5p inhibited sepsis-induced coagulation disorders via targeting NAMPT and inactivating NF-κB pathway.

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Section: Introductionmentioning

confidence: 99%

MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders

Shen

Xie

Peng

et al. 2022

Computational Intelligence and Neuroscience

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“…Previous studies have reported that the liver RBP, HuR, regulates lipid homeostasis in response to a highfat diet (28), and HuR promoted miRNA-mediated up-regulation of NFI-A protein expression in Myeloidderived suppressor cells (MDSCs) and enhanced resistance to uncontrolled infection in septic mice (29), HuR de ciency leads to in ammation and brosis of liver (30). The cold-inducible RBP, CIRP, induces in ammatory responses in hemorrhagic shock and sepsis (31) and activation of splenic T cells dependent on the TLR4 (32).…”

Section: Discussionmentioning

confidence: 99%

Regulation of alternative splicing of lipid metabolism genes in sepsis-induced liver damage by RNA-binding proteins

Abuduaini,

Jiyuan,

Rehati

et al. 2024

Preprint

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Background:RNA binding proteins (RBPs) have the potential for transcriptional regulation in sepsis-induced liver injury, but precise functions remain unclear. Aim: To conduct a genome-wide expression analysis of RBPs and illuminate changes in regulation of alternative splicing in sepsis-induced liver injury. Method: RNA-seq data on "sepsis and liver" from the publicly available NCBI dataset was analyzed, and differentially expressed RBPs and alternative splicing events (ASEs) in 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. Result: 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 upregulated and 408 downregulated, to be identified. DEGs were similar in both CLP and CLPDCA mice. A further 67 upregulated and 58 downregulated DEGS were identified by comparison of sham and CLPDCA groups. GO functional analysis showed DEGs to be enriched in immune and inflammatory-related processes and KEGG analysis showed that lipid metabolism-related pathways were downregulated. 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 shown to be enriched in lipid metabolic and immune /inflammatory-related processes by GO functional analysis. 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. Conclusion: 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.

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

Abuduaini,

Jiyuan,

Rehati

et al. 2024

Inflammation

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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.

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HuR promotes miRNA-mediated upregulation of NFI-A protein expression in MDSCs during murine sepsis

Cited by 3 publications

References 47 publications

MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders

MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders

Regulation of alternative splicing of lipid metabolism genes in sepsis-induced liver damage by RNA-binding proteins

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

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