Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways

Wu, Wenrun; Bao, Wenzhen; Chen, Xiaoli; Lu, Yushi; Ji, Fang; Liu, Jiwen; Peng, Sheng; Pi, Jingjiang; Tomlinson, Brain; Chan, Paul; Zhang, Qi; Zhang, Lin; Liu, Zhongmin; Liu, Jie; Zhang, Yuzhen; Zhuang, Tao

doi:10.1016/j.redox.2023.102775

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…Recent research has demonstrated that CMPK2 is essential for NLRP3 activation and the production of IL‐1β 19 . The NLRP3 receptor, ASC, and caspase‐1 make up the NLRP3 inflammasome complex.…”

Section: Resultsmentioning

confidence: 99%

“…Recent research has demonstrated that CMPK2 is essential for NLRP3 activation and the production of IL-1β. 19 The NLRP3 receptor, ASC, and caspase-1 make up the NLRP3 inflammasome complex. The highly IL-1β and IL-18 were stimulated by the activation of the NLRP3 inflammasome to start a potent inflammatory cascade that resulted in pyroptosis.…”

Section: Nlrp3 Activation After Rsv Infection Is Influenced By Cmpk2mentioning

confidence: 99%

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Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses

Tang,

Mao,

Ruan

et al. 2024

Journal of Medical Virology

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Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS‐CoV‐2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS‐CoV‐2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)‐1β and IL‐18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.

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Section: Resultsmentioning

confidence: 99%

Section: Nlrp3 Activation After Rsv Infection Is Influenced By Cmpk2mentioning

confidence: 99%

Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses

Tang,

Mao,

Ruan

et al. 2024

Journal of Medical Virology

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“…In peripheral system disorders, pharmacological interventions or gene knockout/knockdown of CMPK2 have demonstrated therapeutic effects on a series of inflammation-associated diseases, including ARDS, atherosclerosis, oral ulcer healing, and liver ischemia/reperfusion injury. 21 , 22 , 23 , 59 The sterile inflammation mediated by DAMPs is a crucial component in the pathophysiology after stroke; ATP, HMGB-1, MRP8 (S100A8), and MRP14 (S100A9) may be promising DAMPs to promote CMPK2 upregulation in the brain after stroke, which is worthy of further investigation. Nevertheless, the precise function of CMPK2 in neuroinflammation of central nervous system disorders remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke

Guan,

Zhu,

Song

et al. 2024

Cell Reports Medicine

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“…By performing DEGs analysis, 479 up regulated and 479 down regulated DEGs were successfully identified (|logFC| > 0.512 for up regulated genes, |logFC| < -0.831 for down regulated genes and adjust P-value < .05), respectively. Involvement of SLCO1A2 molecule) [315], DACH1 [316], PNPLA3 [317], FGF9 [192], SLC7A11 [193], SGPP1 [318], VIP (vasoactive intestinal peptide) [319], KCNJ2 [320], KL (klotho) [321], SMAD6 [135], BMPR2 [322], APOA1 [323], CALCRL (calcitonin receptor like receptor) [324], INSIG1 [325], RASGRF1 [198], LRRK2 [326], TLR3 [327], ADRB1 [328], SLC22A3 [329], CA2 [330], SNX10 [331], LIFR (LIF receptor subunit alpha) [332], TLR8 [333], CMPK2 [334], GATA3 [335], RSPO2 [336], CCR2 [205], NEK7 [337], TLR7 [338], BEX1 [339], EFNB2 [340], CAV1 [341], ARRB1 [342], TRPC3 [343], CR1 [344], PEG10 [345], DLL4 [346], MEFV (MEFV innate immuity regulator, pyrin) [347], TFPI (tissue factor pathway inhibitor) [348], EPAS1 [349], FADS1 [215], DKK2 [350], CACNA2D2 [351], DPP6 [352]…”

Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analysis of DEGs were performed. Then, a protein protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst database was used to construct the targeted microRNAs (miRNAs) and transcription factors (TFs) of the hub genes. Finally receiver operating characteristic (ROC) curve analysis was used to validates the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 and EFHC2 were selected. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways

Cited by 8 publications

References 33 publications

Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses

Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses

Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

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