RGD Reference Report - BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy. - Rat Genome Database

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BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

Authors: Shahid, M  Spagnolli, E  Ernande, L  Thoonen, R  Kolodziej, SA  Leyton, PA  Cheng, J  Tainsh, RE  Mayeur, C  Rhee, DK  Wu, MX  Scherrer-Crosbie, M  Buys, ES  Zapol, WM  Bloch, KD  Bloch, DB 
Citation: Shahid M, etal., Am J Physiol Heart Circ Physiol. 2016 Apr 15;310(8):H984-94. doi: 10.1152/ajpheart.00879.2015. Epub 2016 Feb 12.
RGD ID: 11526363
Pubmed: PMID:26873969   (View Abstract at PubMed)
PMCID: PMC4867336   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpheart.00879.2015   (Journal Full-text)

Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction ofId1gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP2Humanangiotensin II increases expression ISOBmp2 (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
BMP4Humanangiotensin II increases expression ISOBmp4 (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
Bmp2Ratangiotensin II increases expression ISOBmp2 (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
Bmp2Mouseangiotensin II increases expression EXP angiotensin II increases expression of mRNA in mouse heartRGD 
Bmp4Ratangiotensin II increases expression ISOBmp4 (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
Bmp4Mouseangiotensin II increases expression EXP angiotensin II increases expression of mRNA in mouse heartRGD 
ID1Humanangiotensin II increases expression ISOId1 (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
Id1Ratangiotensin II increases expression ISOId1 (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
Id1Mouseangiotensin II increases expression EXP angiotensin II increases expression of mRNA in mouse heartRGD 
NPPAHumanangiotensin II increases expression ISONppa (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
NPPBHumanangiotensin II increases expression ISONppb (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
NppaRatangiotensin II increases expression ISONppa (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
NppaMouseangiotensin II increases expression EXP angiotensin II increases expression of mRNA in mouse heartRGD 
NppbRatangiotensin II increases expression ISONppb (Mus musculus)angiotensin II increases expression of mRNA in mouse heartRGD 
NppbMouseangiotensin II increases expression EXP angiotensin II increases expression of mRNA in mouse heartRGD 
BMP2Humanisoprenaline increases expression ISOBmp2 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
BMP4Humanisoprenaline increases expression ISOBmp4 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
BMP7Humanisoprenaline increases expression ISOBmp7 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp2Mouseisoprenaline increases expression ISOBmp2 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp2Ratisoprenaline increases expression EXP isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp4Mouseisoprenaline increases expression ISOBmp4 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp4Ratisoprenaline increases expression EXP isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp7Ratisoprenaline increases expression EXP isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp7Mouseisoprenaline increases expression ISOBmp7 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
ID1Humanisoprenaline increases expression ISOId1 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Id1Mouseisoprenaline increases expression ISOId1 (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Id1Ratisoprenaline increases expression EXP isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NPPAHumanisoprenaline increases expression ISONppa (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NPPBHumanisoprenaline increases expression ISONppb (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppaMouseisoprenaline increases expression ISONppa (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppaRatisoprenaline increases expression EXP isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppbMouseisoprenaline increases expression ISONppb (Rattus norvegicus)isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppbRatisoprenaline increases expression EXP isoprenaline increases expression of mRNA in neonatal rat cardiomyocytesRGD 
BMP2Humanphenylephrine increases expression ISOBmp2 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
BMP4Humanphenylephrine increases expression ISOBmp4 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
BMP7Humanphenylephrine increases expression ISOBmp7 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp2Mousephenylephrine increases expression ISOBmp2 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp2Ratphenylephrine increases expression EXP phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp4Mousephenylephrine increases expression ISOBmp4 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp4Ratphenylephrine increases expression EXP phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp7Mousephenylephrine increases expression ISOBmp7 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Bmp7Ratphenylephrine increases expression EXP phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
ID1Humanphenylephrine increases expression ISOId1 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Id1Mousephenylephrine increases expression ISOId1 (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
Id1Ratphenylephrine increases expression EXP phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NPPAHumanphenylephrine increases expression ISONppa (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NPPBHumanphenylephrine increases expression ISONppb (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppaMousephenylephrine increases expression ISONppa (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppaRatphenylephrine increases expression EXP phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppbMousephenylephrine increases expression ISONppb (Rattus norvegicus)phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 
NppbRatphenylephrine increases expression EXP phenylephrine increases expression of mRNA in neonatal rat cardiomyocytesRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Objects Annotated

Genes (Rattus norvegicus)
Bmp2  (bone morphogenetic protein 2)
Bmp4  (bone morphogenetic protein 4)
Bmp7  (bone morphogenetic protein 7)
Id1  (inhibitor of DNA binding 1)
Nppa  (natriuretic peptide A)
Nppb  (natriuretic peptide B)
Smad1  (SMAD family member 1)
Smad4  (SMAD family member 4)

Genes (Mus musculus)
Bmp2  (bone morphogenetic protein 2)
Bmp4  (bone morphogenetic protein 4)
Bmp7  (bone morphogenetic protein 7)
Id1  (inhibitor of DNA binding 1, HLH protein)
Nppa  (natriuretic peptide type A)
Nppb  (natriuretic peptide type B)

Genes (Homo sapiens)
BMP2  (bone morphogenetic protein 2)
BMP4  (bone morphogenetic protein 4)
BMP7  (bone morphogenetic protein 7)
ID1  (inhibitor of DNA binding 1)
NPPA  (natriuretic peptide A)
NPPB  (natriuretic peptide B)


Additional Information