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Apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent
Yiyuan Yang1, Kai Zhang1, Shifang Huang1
1School of Pharmaceutical Science, Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
Insights
Apelin-13 triggers cardiac hypertrophy by activating the Pannexin-1/P2X7 pathway, which enhances FAM134B-dependent reticulophagy in cardiomyocytes. This mechanism offers new insights into heart disease progression and potential therapeutic targets.
Area of Science:
- Cardiovascular Biology
- Cell Signaling
- Molecular Mechanisms of Disease
Background:
- Cardiac hypertrophy is a major cause of heart disease globally.
- Apelin-13, a peptide, is known to induce cardiomyocyte hypertrophy via autophagy.
- The specific role of apelin-13 in regulating reticulophagy during hypertrophy was not understood.
Purpose of the Study:
- To elucidate the precise mechanism by which apelin-13 regulates reticulophagy in cardiomyocyte hypertrophy.
- To investigate the involvement of the Pannexin-1/P2X7 signaling pathway and FAM134B in this process.
Main Methods:
- Cellular and molecular biology techniques were used to study apelin-13 effects in cardiomyocytes.
- Investigated the Pannexin-1/P2X7 axis, extracellular ATP (eATP) levels, and FAM134B expression.
- Assessed the impact of inhibiting these pathways on apelin-13-induced hypertrophy and reticulophagy.
Main Results:
- Apelin-13 induced cardiomyocyte hypertrophy by activating FAM134B-dependent reticulophagy.
- This activation occurred through the Pannexin-1/P2X7 signaling pathway, involving Pannexin-1 hemichannel opening and increased eATP.
- Inhibiting the Pannexin-1/P2X7 axis or FAM134B-dependent reticulophagy reversed the hypertrophy.
Conclusions:
- Apelin-13, acting through its receptor APJ, induces cardiomyocyte hypertrophy.
- The mechanism involves the activation of the Pannexin-1/P2X7 axis, leading to increased extracellular ATP and subsequent FAM134B-dependent reticulophagy.
- Targeting this pathway may offer a novel therapeutic strategy for cardiac hypertrophy.
Abstract:
Cardiac hypertrophy is a leading cause of cardiac morbidity and mortality worldwide. Apelin is the endogenous ligand for the G protein-coupled receptor, APJ. Previously, we have revealed that apelin-13 can induce cardiomyocyte hypertrophy by activating the autophagy pathway. However, the precise mechanism through which apelin-13 regulates reticulophagy to participate in cardiomyocyte hypertrophy remains unclear. Herein, we observed that apelin-13-induced cardiomyocyte hypertrophy by activating FAM134B-dependent reticulophagy via the Pannexin-1/P2X7 signal pathway. Furthermore, we found that apelin-13 stimulated the opening of Pannexin-1 hemichannel and increased extracellular ATP (eATP) levels, which activated the P2X7 purinergic receptor. Activation of the Pannexin-1/eATP/P2X7 axis subsequently led to FAM134B-dependent reticulophagy. Moreover, inhibition of the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy reversed apelin-13-induced cardiomyocyte hypertrophy. Based on our present findings, apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.
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