Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy

• Published in: PloS one Vol. 16; no. 8; p. e0255452
• Main Authors: Fernández, Carolina, Torrealba, Natalia, Altamirano, Francisco, Garrido-Moreno, Valeria, Vásquez-Trincado, César, Flores-Vergara, Raúl, López-Crisosto, Camila, Ocaranza, María Paz, Chiong, Mario, Pedrozo, Zully, Lavandero, Sergio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-08-2021; Public Library of Science (PLoS)
• Subjects: AKT protein; Analysis; Animals; Antibodies; Biology and Life Sciences; Cardiology; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomyocytes; Cells, Cultured; Chronic illnesses; Deregulation; Diagnosis; Gene expression; Gene Knockdown Techniques; Growth factors; Health aspects; Heart enlargement; Hypertrophy; Insulin; Insulin-like growth factor 1; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Insulin-Like Peptides; Internal medicine; Kinases; Laboratory animals; Medical research; Medicine; Medicine and Health Sciences; Metabolism; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Pharmaceutical sciences; Phenylephrine; Phosphatase; Phosphorylation; Physical Sciences; Physiology; Polycystic kidney disease 1 protein; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Protein-tyrosine-phosphatase; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Receptors; Signal Transduction; TRPP Cation Channels - genetics; TRPP Cation Channels - metabolism; Tyrosine; Chile; United States > US; Texas; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0255452

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.