Association between polymorphisms in the signal transducer and activator of transcription and dilated cardiomyopathy in the Chinese Han population

Peng, Ying; Zhou, Bin; Wang, Yanyun; Chen, Yu; Li, Hui; Song, Yaping; Zhang, Lin; Li, Rao

doi:10.1007/s11010-011-1057-1

Cited by 9 publications

(4 citation statements)

References 44 publications

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“…rs2293152, which has been reported to be significantly associated with CD in the Japanese population (Sato et al, 2009), was associated with susceptibility to UC in the Chinese Han population in this study. rs4796793, which has been reported to be associated with dilated cardiomyopathy in the Chinese Han population (Peng et al, 2012), did not show significant association with UC when studied in the UC patient and normal control groups.…”

Section: Discussionmentioning

confidence: 67%

Association between STAT3 gene polymorphisms and ulcerative colitis susceptibility: a case-control study in the Chinese Han population

Wang¹,

Zt²,

Hx³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Ulcerative colitis (UC) is a chronic inflammation of the large intestine. The aim of this study was to investigate the association of two polymorphisms in STAT3 with the risk of UC development in the Chinese Han population. This is a hospital-based case-control study involving 56 UC patients and 274 controls. Genotyping was performed using the polymerase chain reaction with sequence-specific primers (PCR- SSP) method. Statistical analyses were conducted using logistic regression and genotype risk score. Overall, there was a significant difference between patients and controls in the genotype distribution of rs2293152 (P = 0.044). The risk for UC associated with the rs2293152-G mutant allele was increased (odds ratio = 2.76; 95% confidence interval = 1.06-7.24) under the dominant model. However, we failed to find any obvious differences in the rs4796793 genotype or allele distributions between the UC patients and controls, and did not detect any significant association of the rs4796793 polymorphism with UC across different genetic models of inheritance. Our study implies that the STAT3 rs2293152 polymorphism may be associated with the occurrence of UC and might be used as a predictive factor for UC in the Chinese Han population.

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Section: Discussionmentioning

confidence: 67%

Association between STAT3 gene polymorphisms and ulcerative colitis susceptibility: a case-control study in the Chinese Han population

Wang¹,

Zt²,

Hx³

et al. 2014

Genet. Mol. Res.

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“…Similar to NRG‐1 and ERBB4 (De Keulenaer et al , 2019), STAT5b has previously been proposed to have role in the molecular pathogenesis of heart failure. Indeed, a polymorphism in the exon 1 of the STAT5B gene has been associated with the risk for dilated cardiomyopathy (Peng et al , 2012). Here, we identified differential regulation of the NRG‐1/ERBB4/DNM2/STAT5b signaling in clinical samples of pathological cardiac hypertrophy independent of the etiology.…”

Section: Discussionmentioning

confidence: 99%

STAT5bis a key effector ofNRG‐1/ERBB4‐mediated myocardial growth

et al. 2023

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The growth factor Neuregulin‐1 (NRG‐1) regulates myocardial growth and is currently under clinical investigation as a treatment for heart failure. Here, we demonstrate in several in vitro and in vivo models that STAT5b mediates NRG‐1/EBBB4‐stimulated cardiomyocyte growth. Genetic and chemical disruption of the NRG‐1/ERBB4 pathway reduces STAT5b activation and transcription of STAT5b target genes Igf1, Myc, and Cdkn1a in murine cardiomyocytes. Loss of Stat5b also ablates NRG‐1‐induced cardiomyocyte hypertrophy. Dynamin‐2 is shown to control the cell surface localization of ERBB4 and chemical inhibition of Dynamin‐2 downregulates STAT5b activation and cardiomyocyte hypertrophy. In zebrafish embryos, Stat5 is activated during NRG‐1‐induced hyperplastic myocardial growth, and chemical inhibition of the Nrg‐1/Erbb4 pathway or Dynamin‐2 leads to loss of myocardial growth and Stat5 activation. Moreover, CRISPR/Cas9‐mediated knockdown of stat5b results in reduced myocardial growth and cardiac function. Finally, the NRG‐1/ERBB4/STAT5b signaling pathway is differentially regulated at mRNA and protein levels in the myocardium of patients with pathological cardiac hypertrophy as compared to control human subjects, consistent with a role of the NRG‐1/ERBB4/STAT5b pathway in myocardial growth.

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“…Similar to NRG-1 and ERBB4 47 , STAT5b has previously been proposed to have role in the molecular pathogenesis of heart failure. Indeed, a polymorphism in the exon 1 of the STAT5B gene has been associated with the risk for dilated cardiomyopathy 53 . Here we identified differential regulation of the NRG-1/ERBB4/DNM2/STAT5b signaling in clinical samples of pathological cardiac hypertrophy independent of the etiology.…”

Section: Discussionmentioning

confidence: 99%

STAT5b is a key effector of NRG-1/ERBB4-mediated cardiomyocyte growth

Vaparanta

Jokilammi

Paatero

et al. 2022

Preprint

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The growth factor neuregulin-1 (NRG-1) regulates hypertrophic and hyperplastic myocardial growth and is currently under clinical investigation as a treatment for heart failure. We have previously demonstrated that an isoform of the NRG-1 receptor ERBB4 (ERBB4 JM-b) expressed in cardiomyocytes selectively regulates the activation of STAT5b. To explore the role of STAT5b in NRG-1/EBBB4 mediated cardiomyocyte growth, several in vitro and in vivo models were utilized. The downregulation of NRG-1/ERBB4 signaling consistently reduced STAT5b activation and transcription of STAT5b target genes Igf1, Myc and Cdkn1a in murine in vitro and in vivo models of myocardial growth. Stat5b knock-down in primary cardiomyocytes ablated NRG-1-induced cardiomyocyte hypertrophy. Stat5b was activated during NRG-1-induced hyperplastic myocardial growth and chemical inhibition of the Nrg-1/Erbb4 pathway led to the loss of myocardial growth and Stat5 activation in zebrafish embryos. Moreover, CRISPR/Cas9-mediated knock-down of stat5b in zebrafish embryos resulted in reduced myocardial growth and heart failure as indicated by reduced ventricular ejection fraction. Dynamin-2 was discovered to control the cell surface localization of ERBB4 and the chemical inhibition of dynamin-2 downregulated NRG-1/ERBB4/STAT5b signaling in models of hypertrophic and hyperplastic myocardial growth. Finally, the activation of the NRG-1/ERBB4/STAT5b signaling pathway was explored in clinical samples representing pathological cardiac hypertrophy. The NRG-1/ERBB4/STAT5b signaling pathway was differentially regulated both at the mRNA and protein levels in the myocardium of patients with pathological cardiac hypertrophy as compared to myocardium of control subjects. These results establish the role for STAT5b, and dynamin-2 in NRG-1/ERBB4-mediated myocardial growth.

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Association between polymorphisms in the signal transducer and activator of transcription and dilated cardiomyopathy in the Chinese Han population

Cited by 9 publications

References 44 publications

Association between STAT3 gene polymorphisms and ulcerative colitis susceptibility: a case-control study in the Chinese Han population

Association between STAT3 gene polymorphisms and ulcerative colitis susceptibility: a case-control study in the Chinese Han population

STAT5bis a key effector ofNRG‐1/ERBB4‐mediated myocardial growth

STAT5b is a key effector of NRG-1/ERBB4-mediated cardiomyocyte growth

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