Common Genetic Variants of theBMP4,BMPR1A,BMPR1B, andACVR1Genes, Left Ventricular Mass, and Other Parameters of the Heart in Newborns

Gorący, Iwona; Safranow, Krzysztof; Dawid, Grażyna; Skonieczna-Żydecka, Karolina; Kaczmarczyk, Mariusz; Gorący, Jarosław; Łoniewska, Beata; Ciechanowicz, Andrzej

doi:10.1089/gtmb.2012.0164

Cited by 10 publications

(12 citation statements)

References 48 publications

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“…We assessed transcripts for BMPR1A, BMPR1B , and BMPR2 , the receptors for BMP4 (Feng et al, 2014; Goracy et al, 2012; Miyazono et al, 2010; van Wijk et al, 2007). Using whole-mount ISH, we localized receptor transcripts in basilar papillae from chicks that received no ototoxin using probes described previously (Kawakami et al, 1996; Zou et al, 1997; Hyer et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium

et al. 2018

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Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics. In mature basilar papillae, BMP4 mRNA is highly expressed in hair cells, but not in hair cell progenitors (supporting cells). Supporting cells transcribe genes encoding receptors for BMP4 (BMPR1A, BMPR1B, and BMPR2) and effectors of BMP4 signaling (ID transcription factors). Following hair cell destruction, BMP4 transcripts are lost from the sensory epithelium. Using organotypic cultures, we demonstrate that treatments with BMP4 during hair cell destruction prevent supporting cells from upregulating expression of the pro-hair cell transcription factor ATOH1, entering the cell cycle, and fully transdifferentiating into hair cells, but they do not induce cell death. By contrast, noggin, a BMP4 inhibitor, increases numbers of regenerated hair cells. These findings demonstrate that BMP4 antagonizes hair cell regeneration in the chicken basilar papilla, at least in part by preventing accumulation of ATOH1 in hair cell precursors.

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Section: Resultsmentioning

confidence: 99%

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium

et al. 2018

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“…Presence of the 455C allele of BMP4 and the 8474 T allele of ACVR1 gene was significantly associated with decreased left ventricular ejection fraction (LVEF) (p = 0.0004 and p = 0.046, respectively). The 455C allele of BMP4 plays a role as significant predictors for decreased LVEF in newborns in newborns [ 33 ]. In this study, we found that the single nucleotide polymorphism of 6007C > T is significantly associated with the incidence of LVH in hypertensive patients, suggesting this genetic polymorphism can be used as molecular marker for LVH development.…”

Section: Discussionmentioning

confidence: 99%

The association between BMP4 gene polymorphism and its serum level with the incidence of LVH in hypertensive patients

Yang²,

Zeng

et al. 2015

J Transl Med

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BackgroundBone morphogenic proteins 4 (BMP4) is associated with cardiac remodeling under different conditions. However, the role of BMP4 and its gene polymorphism in the incidence of left ventricular hypertrophy (LVH) in hypertensive patients remains unknown.MethodsA total of 1265 patients diagnosed with essential hypertension (EH) were recruited. Patients were assigned to LVH+ (n = 420) and LVH- (n = 845) groups. serum BMP4 level was measured and two single nucleotide polymorphism (SNPs) polymorphisms, 6007C > T and -5826G > A of BMP4 gene were genotyped. We also inhibited the BMP4 by small interfering RNA (siRNA). The effect of BMP4 on the hypertrophic response in Human Cardiomyocytes AC16 cells was studied.ResultsWe found that the 6007C > T polymorphism of the BMP4 gene and the serum BMP4 level were significantly associated with the risk to develop LVH. With TT as reference, multivariate logistic regression analysis showed the 6007CC genotype carriers had a higher susceptibility to LVH incidence (adjusted OR = 2.65, 95% CI: 1.63-4.31, adjusted P < 0.001). Our in vitro study shows that the BMP4 inhibition in cardiomyocyte by si-RNA technique significantly decreased the Ang II induced cardiomyocyte size and protein content per cell, indicating the importance of BMP4 in the cardiomyocyte hypertrophy.ConclusionCollectively, our data suggest that both the 6007C > T of the BMP4 gene and the serum BMP4 level may be used as potential marker for LVH incidence among the EH patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0368-x) contains supplementary material, which is available to authorized users.

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“…Abnormalities in a number of genes, the normal expression of which we found dependent on AcvR1 have already been identified as causative of CHD (TBX20(Kirk et al, 2007) and TGFB2(Gao et al, 2012; Lindsay et al, 2012)) , or as potential contributory (TBX2(Pang et al, 2013),TBX3(Chen et al, 2013), BMP4(Goracy et al, 2012), TDGF1(Roessler et al, 2008; Wang et al, 2011) and ISL1(Stevens et al, 2010)) . Even a mildly defective allele of Acvr1 could influence the expression of many genes known to be required for normal heart development and when in combination with other such alleles of these genes account for cases of CHD.…”

Section: Discussionmentioning

confidence: 58%

AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: Implications for myocardial differentiation and regional identity

Thomas

Rajderkar

Lane

et al. 2014

Developmental Biology

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BMP signaling plays an essential role in second heart field-derived heart and arterial trunk development, including myocardial differentiation, right ventricular growth, and interventricular, outflow tract and aortico-pulmonary septation. It is mediated by a number of different BMP ligands, and receptors, many of which are present simultaneously. The mechanisms by which they regulate morphogenetic events and degree of redundancy amongst them have still to be elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in anterior second heart field-derived cell development, and compared it with that of BmpR1a. By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1 plays an essential role in arterial pole morphogenesis, identifying defects in outflow tract wall and cushion morphology that preceded a spectrum of septation defects from double outlet right ventricle to common arterial trunk in mutants. Its absence caused dysregulation in gene expression important for myocardial differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2). Although these defects resemble to some degree those in the equivalent Bmpr1a mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1 locus only partially restored septation in Acvr1 mutants. These data show that both BmpR1a and AcvR1 are needed for normal heart development, in which they play some non-redundant roles, and refine our understanding of the genetic and morphogenetic processes underlying Bmp-mediated heart development important in human congenital heart disease.

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Common Genetic Variants of theBMP4,BMPR1A,BMPR1B, andACVR1Genes, Left Ventricular Mass, and Other Parameters of the Heart in Newborns

Cited by 10 publications

References 48 publications

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium

The association between BMP4 gene polymorphism and its serum level with the incidence of LVH in hypertensive patients

AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: Implications for myocardial differentiation and regional identity

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