Molecular Medicine Nuclear Plakoglobin Is Essential for Differentiation of Cardiac Progenitor Cells to Adipocytes in Arrhythmogenic Right Ventricular Cardiomyopathy
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چکیده
fibro-adiposis, cardiac dysfunction, and premature death. Subcellular protein fractionation and immunofluorescence showed nuclear localization of PG and PG and reduced membrane localization of PG. Coimmunoprecipitation showed reduced binding of PG but not PG to desmosome proteins DSP and DSG2. Transgene PG and PG were expressed in c-Kit :Sca1 cardiac progenitor cells (CPCs) isolated from the hearts of PG and PG by fluorescence activated cell sorting. CPCs isolated from the transgenic hearts
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histology in search of new diagnostic markers. J Cardiovasc Electrophysiol 2011;22: 111–117. 21. Matsuura K, Masuda S, Haraguchi Y, Yasuda N, Shimizu T, Hagiwara N, Zandstra PW, Okano T. Creation of mouse embryonic stem cell-derived cardiac cell sheets. Biomaterials 2011;32:7355–7362. 22. Paige SL, Osugi T, Afanasiev OK, Pabon L, Reinecke H, Murry CE. Endogenous Wnt/beta-catenin signaling is re...
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The phenotypic hallmark of arrhythmogenic right ventricular cardiomyopathy, a genetic disease of desmosomal proteins, is fibroadipocytic replacement of the right ventricle. Cellular origin of excess adipocytes, the responsible mechanism(s) and the basis for predominant involvement of the right ventricle are unknown. We generated 3 sets of lineage tracer mice regulated by cardiac lineage promote...
متن کاملNuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy.
RATIONALE Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease of desmosome proteins characterized by fibroadipogenesis in the myocardium. We have implicated signaling properties of junction protein plakoglobin (PG) in the pathogenesis of ARVC. OBJECTIVE To delineate the pathogenic role of PG in adipogenesis in ARVC. METHODS AND RESULTS We generated mice overexpressing PG, ei...
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