RGD Reference Report - A thrombospondin-1 antagonist of transforming growth factor-beta activation blocks cardiomyopathy in rats with diabetes and elevated angiotensin II. - Rat Genome Database

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A thrombospondin-1 antagonist of transforming growth factor-beta activation blocks cardiomyopathy in rats with diabetes and elevated angiotensin II.

Authors: Belmadani, S  Bernal, J  Wei, CC  Pallero, MA  Dell'italia, L  Murphy-Ullrich, JE  Berecek, KH 
Citation: Belmadani S, etal., Am J Pathol. 2007 Sep;171(3):777-89. Epub 2007 Jul 19.
RGD ID: 2317942
Pubmed: PMID:17640965   (View Abstract at PubMed)
PMCID: PMC1959499   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2007.070056   (Journal Full-text)

In diabetes and hypertension, the induction of increased transforming growth factor-beta (TGF-beta) activity due to glucose and angiotensin II is a significant factor in the development of fibrosis and organ failure. We showed previously that glucose and angiotensin II induce the latent TGF-beta activator thrombospondin-1 (TSP1). Because activation of latent TGF-beta is a major means of regulating TGF-beta, we addressed the role of TSP1-mediated TGF-beta activation in the development of diabetic cardiomyopathy exacerbated by abdominal aortic coarctation in a rat model of type 1 diabetes using a peptide antagonist of TSP1-dependent TGF-beta activation. This surgical manipulation elevates initial blood pressure and angiotensin II. The hearts of these rats had increased TSP1, collagen, and TGF-beta activity, and cardiac function was diminished. A peptide antagonist of TSP1-dependent TGF-beta activation prevented progression of cardiac fibrosis and improved cardiac function by reducing TGF-beta activity. These data suggest that TSP1 is a significant mediator of fibrotic complications of diabetes associated with stimulation of the renin-angiotensin system, and further studies to assess the blockade of TSP1-dependent TGF-beta activation as a potential antifibrotic therapeutic strategy are warranted.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
THBS1HumanExperimental Diabetes Mellitus  ISOThbs1 (Rattus norvegicus) RGD 
Thbs1RatExperimental Diabetes Mellitus  IMP  RGD 
Thbs1MouseExperimental Diabetes Mellitus  ISOThbs1 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Thbs1Ratpositive regulation of transforming growth factor beta production  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Thbs1  (thrombospondin 1)

Genes (Mus musculus)
Thbs1  (thrombospondin 1)

Genes (Homo sapiens)
THBS1  (thrombospondin 1)


Additional Information