Cardiac hypertrophy is the result of responses to various physiological or pathological stimuli. Recently, we showed that polycystin-1 participates in cardiomyocyte hypertrophy elicited by pressure overload and mechanical stress. Interestingly, polycystin-1 knockdown does not affect phenylephrine-induced cardiomyocyte hypertrophy, suggesting that the effects of polycystin-1 are stimulus-dependent. In this study, we aimed to identify the role of polycystin-1 in insulin-like growth factor-1 (IGF-1) signaling in cardiomyocytes. Polycystin-1 knockdown completely blunted IGF-1-induced cardiomyocyte hypertrophy. We then investigated the molecular mechanism underlying this result. We found that polycystin-1 silencing impaired the activation of the IGF-1 receptor, Akt, and ERK1/2 elicited by IGF-1. Remarkably, IGF-1-induced IGF-1 receptor, Akt, and ERK1/2 phosphorylations were restored when protein tyrosine phosphatase 1B was inhibited, suggesting that polycystin-1 knockdown deregulates this phosphatase in cardiomyocytes. Moreover, protein tyrosine phosphatase 1B inhibition also restored IGF-1-dependent cardiomyocyte hypertrophy in polycystin-1-deficient cells. Our findings provide the first evidence that polycystin-1 regulates IGF-1-induced cardiomyocyte hypertrophy through a mechanism involving protein tyrosine phosphatase 1B.

Center for New Drugs for Hypertension Pontificia Universidad Católica de Chile Santiago de Chile Chile

Corporación Centro de Estudios Científicos de las Enfermedades Crónicas Santiago de Chile Chile

Department of Cardiothoracic Surgery Weill Cornell Medical College Cornell University Ithaca New York United States of America

Department of Cardiovascular Sciences DeBakey Heart and Vascular Center Houston Methodist Research Institute Houston Texas United States of America

Division of Cardiology Department of Internal Medicine University of Texas Southwestern Medical Center Dallas Texas United States of America

Facultad de Medicina Programa de Fisiología y Biofísica Instituto de Ciencias Biomédicas Universidad de Chile Santiago de Chile Chile

Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine Advanced Center for Chronic Diseases Universidad de Chile and Pontificia Universidad Católica de Chile Santiago de Chile Chile

Faculty of Medicine Division of Cardiovascular Diseases Pontificia Universidad Católica de Chile Santiago de Chile Chile

Laboratory of Tumour Resistance Institute of Biotechnology of the Czech Academy of Sciences Vestec Czech Republic

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