RNA-binding protein CELF1 promotes cardiac hypertrophy via interaction with PEBP1 in cardiomyocytes

Hu, Xiaomin; Wu, Peng; Liu, Bojiang; Lang, Yuheng; Li, Tong

doi:10.1007/s00441-021-03541-5

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…RKIP negatively regulates NLRP1 activation and NLRP3 and NLRC4-induced inflammatory body formation and plays an important role in the pathogenesis of type 2 diabetes ( 58 ). Overexpression of CUG triplet repeat-binding protein 1 (CELF1) negatively regulates the protein expression of PEBP1, and knocking down PEBP1 expression partially enhances ROS production and the apoptosis rate of neonatal cardiomyocytes ( 59 ). PEBP1 is involved in regulating endothelial cell autophagy and affects atherosclerosis ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques

Ren

et al. 2022

Front. Cardiovasc. Med.

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ObjectivesAbdominal aortic aneurysm (AAA) is a cardiovascular disease with high mortality and pathogenesis closely related to various cell death types, e.g., autophagy, apoptosis and pyroptosis. However, the association between AAA and ferroptosis is unknown.MethodsGSE57691 and GSE98278 dataset were obtained from the Gene Expression Omnibus database, and a ferroptosis-related gene (FRG) set was downloaded from the FerrDb database. These data were normalized, and ferroptosis-related differentially expressed genes (FDEGs, AAA vs. normal samples) were identified using the limma package in R. FRGs expression was analyzed by Gene Set Expression Analysis (GSEA), and FDEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses using the clusterProfiler package in R and ClueGO in Cytoscape. Protein–protein interaction networks were assembled using Cytoscape, and crucial FDEGs were identified using CytoHubba. Critical FDEG transcription factors (TFs) were predicted with iRegulon. FDEGs were verified in GSE98278 set, and key FDEGs in AAA (compared with normal samples) and ruptured AAA (RAAA; compared with AAA samples) were identified. Ferroptosis-related immune cell infiltration and correlations with key genes were analyzed by CIBERSORT. Key FEDGs were reverified in Ang II-induced AAA models of ApoE–/– and CD57B/6J mice by immunofluorescence assay.ResultsIn AAA and normal samples, 40 FDEGs were identified, and the expression of suppressive FRGs was significantly downregulated with GSEA. For FDEGs, the GO terms were response to oxidative stress and cellular response to external stimulus, and the KEGG pathways were the TNF and NOD-like receptor signaling pathways. IL6, ALB, CAV1, PTGS2, NOX4, PRDX6, GPX4, HSPA5, HSPB1, and NCF2 were the most enriched genes in the crucial gene cluster. CEBPG, NFAT5, SOX10, GTF2IRD1, STAT1, and RELA were potential TFs affecting these crucial genes. Ferroptosis-related immune cells involved in AAA formation were CD8+ T, naive CD4+ T, and regulatory T cells (Tregs); M0 and M2 macrophages; and eosinophils. Tregs were also involved in RAAA. GPX4, SLC2A1, and PEBP1 expression was downregulated in both the RAAA and AAA samples. GPX4 and PEBP1 were more important in AAA because they influenced ferroptosis-related immune cell infiltration, and SLC2A1 was more important in RAAA.ConclusionsThis is the first study to show that ferroptosis is crucial to AAA/RAAA formation. The TNF and NOD-like signaling pathways and ferroptosis-related immune cell infiltration play key roles in AAA/RAAA. GPX4 is a key ferroptosis-related gene in AAA. Ferroptosis and related genes might be promising targets in the treatment of AAA/RAAA.

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Section: Discussionmentioning

confidence: 99%

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques

Ren

et al. 2022

Front. Cardiovasc. Med.

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“…Additionally, GSDMD, AIM 2, and COX-2 have recently been identified as a key role in the pathogenesis of sepsis and COVID-19 [ 36 – 38 ]. Celf1 is known as an RNA-binding protein [ 39 ]. Hu et al found that Celf1-deficiency could improve oxidative stress and apoptosis in cardiomyocytes [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice

Yang

Gao

et al. 2022

Inflamm. Res.

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Background and objective Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear. Methods We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis. Results LC–MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1β, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model. Conclusion This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-022-01623-w.

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“…The modification of mRNA after transcription plays a pivotal role in controlling protein expression and the progression of cardiovascular diseases [ 27 , 43 , 44 ]. Previous studies have provided evidence indicating that CELF1 as a regulator of pathological myocardial hypertrophy and apoptosis by directly interacting with the 3' UTR of PEBP1, thereby impeding the activation of the MAPK signaling pathway [ 14 ]. This discovery opens up new possibilities for therapeutic interventions in treatment of hypertrophic cardiomyopathy and heart failure.…”

Section: Celf1 and Related Diseasesmentioning

confidence: 99%

“…CELF1 is involved in many body homeostasis such as development of embryonic and heart, differentiation of bone and adipose tissue, as well as formation germ cells [ 10 – 12 ]. The aberrant expression of CELF1 leads to multiple diseases such as myotonic dystrophy type 1 (DM1) [ 13 ], myocardial hypertrophy [ 14 ]. Extensive genomic and transcriptomic analyses have revealed substantial changes in mutational profiles, copy number variations, and mRNA expression levels of various RNA-binding proteins in numerous tumor types [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review

Qin,

Shi,

Chen

et al. 2024

Cell Mol Biol Lett

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RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid–protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure–activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy. Graphical Abstract

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RNA-binding protein CELF1 promotes cardiac hypertrophy via interaction with PEBP1 in cardiomyocytes

Cited by 9 publications

References 33 publications

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques

Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review

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