RGD Reference Report - BAMBI (BMP and activin membrane-bound inhibitor) protects the murine heart from pressure-overload biomechanical stress by restraining TGF-β signaling. - Rat Genome Database

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BAMBI (BMP and activin membrane-bound inhibitor) protects the murine heart from pressure-overload biomechanical stress by restraining TGF-β signaling.

Authors: Villar, Ana V  García, Raquel  Llano, Miguel  Cobo, Manuel  Merino, David  Lantero, Aquilino  Tramullas, Mónica  Hurlé, Juan M  Hurlé, María A  Nistal, J Francisco 
Citation: Villar AV, etal., Biochim Biophys Acta. 2013 Feb;1832(2):323-35. doi: 10.1016/j.bbadis.2012.11.007. Epub 2012 Nov 17.
RGD ID: 14390160
Pubmed: PMID:23168040   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbadis.2012.11.007   (Journal Full-text)

Left ventricular (LV) pressure overload is a major cause of heart failure. Transforming growth factors-β (TGF-βs) promote LV remodeling under biomechanical stress. BAMBI (BMP and activin membrane-bound inhibitor) is a pseudoreceptor that negatively modulates TGF-β signaling. The present study tests the hypothesis that BAMBI plays a protective role during the adverse LV remodeling under pressure overload. The subjects of the study were BAMBI knockout mice (BAMBI(-/-)) undergoing transverse aortic constriction (TAC) and patients with severe aortic stenosis (AS). We examined LV gene and protein expression of remodeling-related elements, histological fibrosis, and heart morphology and function. LV expression of BAMBI was increased in AS patients and TAC-mice and correlated directly with TGF-β. BAMBI deletion led to a gain of myocardial TGF-β signaling through canonical (Smads) and non-canonical (TAK1-p38 and TAK1-JNK) pathways. As a consequence, the remodeling response to pressure overload in BAMBI(-/-) mice was exacerbated in terms of hypertrophy, chamber dilation, deterioration of long-axis LV systolic function and diastolic dysfunction. Functional remodeling associated transcriptional activation of fibrosis-related TGF-β targets, up-regulation of the profibrotic micro-RNA-21, histological fibrosis and increased metalloproteinase-2 activity. Histological remodeling in BAMBI(-/-) mice involved TGF-βs. BAMBI deletion in primary cardiac fibroblasts exacerbated TGF-β-induced profibrotic responses while BAMBI overexpression in NIH-3T3 fibroblasts attenuated them. Our findings identify BAMBI as a critical negative modulator of myocardial remodeling under pressure overload. We suggest that BAMBI is involved in negative feedback loops that restrain the TGF-β remodeling signals to protect the pressure-overloaded myocardium from uncontrolled extracellular matrix deposition in humans and mice.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BAMBIHumanaortic valve stenosis  IEP protein:increased expression:myocardium:RGD 
BambiRataortic valve stenosis  ISOBAMBI (Homo sapiens)protein:increased expression:myocardium:RGD 
BambiMouseaortic valve stenosis  ISOBAMBI (Homo sapiens)protein:increased expression:myocardium:RGD 
BAMBIHumanVentricular Outflow Obstruction  ISOBambi (Mus musculus)protein:increased expression:myocardium:RGD 
BambiRatVentricular Outflow Obstruction  ISOBambi (Mus musculus)protein:increased expression:myocardium:RGD 
BambiMouseVentricular Outflow Obstruction  IEP protein:increased expression:myocardium:RGD 
BambiMouseVentricular Outflow Obstruction  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bambi  (BMP and activin membrane-bound inhibitor)

Genes (Mus musculus)
Bambi  (BMP and activin membrane-bound inhibitor)

Genes (Homo sapiens)
BAMBI  (BMP and activin membrane bound inhibitor)


Additional Information