FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling

Gao, Weinian; Guo, Na; Zhao, Sen; Chen, Ziying; Zhang, Wenli; Yan, Fang; Liao, Haojie; Chi, Kui

doi:10.1016/j.yexcr.2020.112059

Cited by 21 publications

(16 citation statements)

References 33 publications

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“…F-box and WD repeat domain-containing 7 (FBXW7) is an E3-ubiquitin ligase, which serves as one of the components of the SKP1, CUL1, and F-box protein type ubiquitin ligase (SCF) complex. Previous study identi ed FBWX7 as an important regulator of cardiac hypertrophy [34].…”

Section: Discussionmentioning

confidence: 99%

Piezo Type Mechanosensitive Ion Channel Component 1 is Required for Heart Development in Zebrafish

Liu¹,

Fang²,

Chen³

et al. 2021

Preprint

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PIEZO1 is a non-selective cation channel protein that converts mechanical stimuli into electrochemical signals through mechanical force transmission. In recent years, more and more attention has been paid to its relationship with cardiovascular development and related diseases. However, PIEZO1 is difficult to be used as a therapeutic target due to incomplete study of its related phenotype and mechanism. Starting with the phenotypes of zebrafish at different stages of development, piezo1 knockout zebrafish features decreased heart rate in embryonic stage, increased heart size in 72dpf larvae, as well as ventricular enlargement, passivation and increased immune infiltration in adult stage. Further characterization revealed the relationship between PIEZO1 and AcanA protein at embryonic stage, and hand2 protein at adult stage. Through further RNA-seq analysis, ptpn21 downregulation, shox2 upregulation, itga4 upregulation were used to explain ventricular enlargement, heart rate decrease and immune infiltration increase respectively. Overall, this study provides a theoretical basis for elucidating the mechanism of PIEZO1 in regulating cardiac development.

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Section: Discussionmentioning

confidence: 99%

Piezo Type Mechanosensitive Ion Channel Component 1 is Required for Heart Development in Zebrafish

Liu¹,

Fang²,

Chen³

et al. 2021

Preprint

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“…[85], NOTCH2 [86], LRP1 [87], CLU (clusterin) [88], FCN1 [89], CDKN1A [90], SMAD3 [91], HLA-E [92], PTPRC (protein tyrosine phosphatase receptor type C) [93], MYH9 [94], JAK3 [95], IL6R [96], TIMP1 [97], DOCK8 [98], TNFRSF1B [99], ITGAL (integrin subunit alpha L) [100], CD47 [101], RARA (retinoic acid receptor alpha) [102], DGKD (diacylglycerol kinase delta) [103], PLEK (pleckstrin) [104], PREX1 [105], BSCL2 [106], PANX1 [107], IRF7 [108] [116] were revealed to be expressed in diabetes mellitus, but these genes might be novel targets for GDM. SIX1 [117], GREM1 [118], GHRHR (growth hormone releasing hormone receptor) [119], GPR37L1 [120], CYP2J2 [121], AQP4 [122], ROS1 [123], LBP (lipopolysaccharide binding protein) [124], SGCD (sarcoglycan delta) [133], PTHLH [134], FAP (fibroblast activation protein alpha) [135], THSD7A [136], SHROOM3 [137], ETV1 [138], CYP24A1 [139], SLIT2 [140], GJC1 [141], PPARGC1A [142], TRPM3 [143], IGF1 [144], TRPV6 [145], TLR3 [146], BMP7 [147], DSG2 [148], POSTN (periostin) [149], ENOX1 [150], KCNA7…”

Section: Discussionmentioning

confidence: 99%

“…LGR5 [61], GREM1 [62], GLRA3 [63], NEUROD4 [64], CYP2J2 [65], KCNH6 [66], LBP (lipopolysaccharide binding protein) [67], CXCL14 [68], RGN (regucalcin) [69], NPY2R [70], SERPINB13 [71], WNT5A [72], EDA (ectodysplasin A) [73], HSD11B2 [74], ACVR1C [75], NEUROD1 [76], SLIT2 [77], PPARGC1A [78], IGF1 [79], OSR1 [80], CYP46A1 [81], TLR3 [82], BMP7 [83], SELP (selectin P) [84], HLA-A [85], NOTCH2 [86], LRP1 [87], CLU (clusterin) [88], FCN1 [89], CDKN1A [90], SMAD3 [91], HLA-E [92], PTPRC (protein tyrosine phosphatase receptor type C) [93], MYH9 [94], JAK3 [95], IL6R [96], TIMP1 [97], DOCK8 [98], TNFRSF1B [99], ITGAL (integrin subunit alpha L) [100], CD47 [101], RARA (retinoic acid receptor alpha) [102], DGKD (diacylglycerol kinase delta) [103], PLEK (pleckstrin) [104], PREX1 [105], BSCL2 [106], PANX1 [107], IRF7 [108], NOTCH1 [109], STIM1 [110], TRIM13 [111], LRBA (LPS responsive beige-like anchor protein) [112], CXCR4 [113], MDM4 [114], MYO9B [115] and PDE5A [116] were revealed to be expressed in diabetes mellitus, but these genes might be novel targets for GDM. SIX1 [117], GREM1 [118], GHRHR (growth hormone releasing hormone receptor) [119], GPR37L1 [120], CYP2J2 [121], AQP4 [122], ROS1 [123], LBP (lipopolysaccharide binding protein) [124], SGCD (sarcoglycan delta) [125], CXCL14 [126], RGN (regucalcin) [127], F9 [128], KCND2 [129], AZGP1 [130], HAS2 [131], CNTN4 [132], WNT5A [...…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy. Numerous biomarkers have been identified that are linked with the occurrence and development of GDM. The aim of this investigation was to identify differentially expressed genes (DEGs) in GDM using a bioinformatics approach to elucidate their molecular pathogenesis. GDM associated expression profiling by high throughput sequencing dataset (GSE154377) was obtained from Gene Expression Omnibus (GEO) database including 28 normal pregnancy samples and 33 GDM samples. DEGs were identified using DESeq2. The gene ontology (GO) and REACTOME pathway enrichments of DEGs were performed by g:Profiler. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into modules using the PEWCC1 algorithm. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were performed with the miRNet database and NetworkAnalyst database. Receiver Operating Characteristic (ROC) analyses was conducted to validate the hub genes. A total of 953 DEGs were identified, of which 478 DEGs were up regulated and 475 DEGs were down regulated. Furthermore, GO and REACTOME pathway enrichment analysis demonstrated that these DEGs were mainly enriched in multicellular organismal process, cell activation, formation of the cornified envelope and hemostasis. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB were identified as key genes in the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB in GDM were validated using ROC analysis. This investigation provides further insights into the molecular pathogenesis of GDM, which might facilitate the diagnosis and treatment of GDM.

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“…Cardiomyocytes were isolated from 1 to 3‐day old neuronal rat hearts as described previously (Gao et al, 2020a; Tang et al, 2016). Cardiomyocytes were cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco; #C11965500BT) supplemented with 10% FBS (Gibco; #A3840001) and BrdU (Sigma; #B5002) to repress fibroblast proliferation.…”

Section: Methodsmentioning

confidence: 99%

GPR39 promotes cardiac hypertrophy by regulating the AMPK–mTOR pathway and protein synthesis

Liao

Gao

et al. 2021

Cell Biology International

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Hypertrophic growth of the cardiomyocytes is one of the core mechanisms underlying cardiac hypertrophy. However, the mechanism underlying cardiac hypertrophy remains not fully understood. Here we provided evidence that G protein‐coupled receptor 39 (GPR39) promotes cardiac hypertrophy via inhibiting AMP‐activated protein kinase (AMPK) signaling. GRP39 expression is overexpressed in hypertrophic hearts of humans and transverse aortic constriction (TAC)‐induced cardiac hypertrophy in mice. In neonatal cardiomyocytes, adenovirus‐mediated overexpression of GPR39 promoted angiotensin II‐induced cardiac hypertrophy, while GPR39 knockdown repressed hypertrophic response. Adeno‐associated virus 9‐mediated knockdown of GPR39 suppressed TAC‐induced decline in fraction shortening and ejection fraction, increase in heart weight and cardiomyocyte size, as well as overexpression of hypertrophic fetal genes. A mechanism study demonstrated that GPR39 repressed the activation of AMPK to activate the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β‐1 (S6K1), subsequently promoted de novo protein synthesis. Inhibition of mTOR with rapamycin blocked the effects of GPR39 overexpression on protein synthesis and repressed cardiac hypertrophy. Collectively, our findings demonstrated that GPR39 promoted cardiac hypertrophy via regulating the AMPK–mTOR–S6K1 signaling pathway, and GRP39 can be targeted for the treatment of cardiac hypertrophy.

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FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling

Cited by 21 publications

References 33 publications

Piezo Type Mechanosensitive Ion Channel Component 1 is Required for Heart Development in Zebrafish

Piezo Type Mechanosensitive Ion Channel Component 1 is Required for Heart Development in Zebrafish

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

GPR39 promotes cardiac hypertrophy by regulating the AMPK–mTOR pathway and protein synthesis

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