RGD Reference Report - Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice. - Rat Genome Database

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Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice.

Authors: Shen, Jin-Song  Meng, Xing-Li  Wight-Carter, Mary  Day, Taniqua S  Goetsch, Sean C  Forni, Sabrina  Schneider, Jay W  Liu, Zhi-Ping  Schiffmann, Raphael 
Citation: Shen JS, etal., Hum Mol Genet. 2015 Jun 1;24(11):3181-91. doi: 10.1093/hmg/ddv070. Epub 2015 Feb 20.
RGD ID: 11576234
Pubmed: (View Article at PubMed) PMID:25701874
DOI: Full-text: DOI:10.1093/hmg/ddv070

Fabry disease is caused by deficient activity of lysosomal enzyme a-galactosidase A. The enzyme deficiency results in intracellular accumulation of glycosphingolipids, leading to a variety of clinical manifestations including hypertrophic cardiomyopathy and renal insufficiency. The mechanism through which glycosphingolipid accumulation causes these manifestations remains unclear. Current treatment, especially when initiated at later stage of the disease, does not produce completely satisfactory results. Elucidation of the pathogenesis of Fabry disease is therefore crucial to developing new treatments. We found increased activity of androgen receptor (AR) signaling in Fabry disease. We subsequently also found that blockade of AR signaling either through castration or AR-antagonist prevented and reversed cardiac and kidney hypertrophic phenotype in a mouse model of Fabry disease. Our findings implicate abnormal AR pathway in the pathogenesis of Fabry disease and suggest blocking AR signaling as a novel therapeutic approach.

Annotation

Disease Annotations    
Fabry disease  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ar  (androgen receptor)

Genes (Mus musculus)
Ar  (androgen receptor)

Genes (Homo sapiens)
AR  (androgen receptor)


Additional Information