Open AccessPolycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy
Author(s) -
Carolina Fernández,
Natalia Torrealba,
Francisco Altamirano,
Valeria Garrido-Moreno,
César VásquezTrincado,
Raúl Flores-Vergara,
Camila López-Crisosto,
María Paz Ocaranza,
Mario Chiong,
Zully Pedrozo,
Sergio Lavandero
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0255452
Subject(s) - medicine , endocrinology , muscle hypertrophy , protein tyrosine phosphatase , insulin like growth factor , gene knockdown , protein kinase b , phosphatase , microbiology and biotechnology , biology , growth factor , signal transduction , chemistry , receptor , phosphorylation , apoptosis , biochemistry
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.