title: Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice.
abstract: Fabry disease is caused by deficient activity of lysosomal enzyme α-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.
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX 75226, USA jinsong.shen@baylorhealth.edu.
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Shen
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX 75226, USA.
authors.forename: Xing-Li
authors.initials: XL
authors.lastname: Meng
authors.affiliation: Animal Resources Center Diagnostic Laboratory and.
authors.forename: Mary
authors.initials: M
authors.lastname: Wight-Carter
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX 75226, USA.
authors.forename: Taniqua S
authors.initials: TS
authors.lastname: Day
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Goetsch
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX 75226, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Forni
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Schneider
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX 75226, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D000795:Fabry Disease / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen