Maresin-1 induces cardiomyocyte hypertrophy through IGF-1 paracrine pathway

Tri Wahyuni, Arisa Kobayashi, Shota Tanaka, Yoshiaki Miyake, Ayaha Yamamoto, Anton Bahtiar, Shota Mori, Yusuke Kametani, Masashi Tomimatsu, Kotaro Matsumoto, Makiko Maeda, Masanori Obana, Yasushi Fujio

Research output: Contribution to journalArticlepeer-review

Abstract

The resolution of inflammation is closely linked with tissue repair. Recent studies have revealed that macrophages suppress inflammatory reactions by producing lipid mediators, called specialized proresolving mediators (SPMs); however, the biological significance of SPMs in tissue repair remains to be fully elucidated in the heart. In this study, we focused on maresin-1 (MaR1) and examined the reparative effects of MaR1 in cardiomyocytes. The treatment with MaR1 increased cell size in cultured neonatal rat cardiomyocytes. Since the expression of fetal cardiac genes was unchanged by MaR1, physiological hypertrophy was induced by MaR1. SR3335, an inhibitor of retinoic acid-related orphan receptor a (RORa), mitigated MaR1-induced cardiomyocyte hypertrophy, consistent with the recent report that RORa is one of MaR1 receptors. Importantly, in response to MaR1, cardiomyocytes produced IGF-1 via RORa. Moreover, MaR1 activated phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and wortmannin, a PI3K inhibitor, or triciribine, an Akt inhibitor, abrogated MaR1-induced cardiomyocyte hypertrophy. Finally, the blockade of IGF-1 receptor by NVP-AEW541 inhibited MaR-1-induced cardiomyocyte hypertrophy as well as the activation of PI3K/Akt pathway. These data indicate that MaR1 induces cardiomyocyte hypertrophy through RORa/IGF-1/PI3K/Akt pathway. Considering that MaR1 is a potent resolving factor, MaR1 could be a key mediator that orchestrates the resolution of inflammation with myocardial repair.

Original languageEnglish
Pages (from-to)C82-C93
JournalAmerican Journal of Physiology - Cell Physiology
Volume321
Issue number1
DOIs
Publication statusPublished - Jul 2021

Keywords

  • Cardiomyocyte
  • Hypertrophy
  • IGF-1
  • Maresin-1
  • Physiology

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