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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1541869
This article is part of the Research Topic Advancements in Therapeutic Strategies for Skeletal Muscle and Cardiovascular Diseases: Integrating Innovative Approaches for Enhanced Outcomes View all articles
ELABELA promotes the migration and homing of bone marrow mesenchymal stem cells to myocardial injury sites through the ERK1/2/miR-299a-5p/Exo70 pathway
Provisionally accepted
Jing-Yu Hou 1 Hao Wu 2 Shuang-Mei Li 1
Xiaojing Li 1 Shu-Jun Yang 1 Xu-Xiang Chen 1 Chang-Qing Zhou 1 Hui-Bao Long 1
Haidong Wu 1 Jia-Ying Fu 1
Yajie Guo 1*
Tong Wang 3*- 1 Department of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- 2 Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
- 3 The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
Abstract：Bone marrow mesenchymal stem cells (BMSCs) hold promise for repairing myocardial injury following acute myocardial infarction (AMI), but their clinical application is hindered by poor migration, homing efficiency, and survival rates. Previously, we demonstrated that ELABELA (ELA), a small peptide, enhances the survival of rat BMSCs under hypoxiareoxygenation (H/R) conditions by activating ERK1/2. However, the role of ELA in promoting BMSCs migration and homing to injured cardiomyocytes remains unclear. To investigate this, we isolated primary BMSCs and neonatal rat ventricular myocytes (NRVMs), exposing NRVMs to H/R conditions to simulate the AMI microenvironment. We evaluated BMSCs migration using transwell assays and chemotaxis assays in vitro, and conducted in vivo studies using a rat myocardial infarction/reperfusion injury (MI/RI) model with DIR-labeled BMSCs.Cardiac repair was assessed through fluorescence imaging, echocardiography, and histological analysis. Transcriptome sequencing revealed upregulation of Exo70 in ELA-pretreated BMSCs, which promoted F-actin polymerization and migration. Overexpression of miR-299a-5p reduced Exo70 expression and impaired BMSCs migration. ELA also activated ERK1/2 phosphorylation, while inhibition of ERK1/2 with U0126 abrogated F-actin polymerization and migration, increasing miR-299a-5p levels and reducing Exo70. These findings indicate that ELA enhances BMSCs migration and homing to injured cardiomyocytes by activating the APJ receptor, promoting ERK1/2 phosphorylation, downregulating miR-299a-5p, and upregulating Exo70, providing a potential therapeutic strategy for improving stem cell-based cardiac repair.
Keywords: Elabela, Bone marrow mesenchymal stem cells, migration and homing, Myocardial injury, Exo70
Received: 08 Dec 2024; Accepted: 14 Jan 2025.
Copyright: © 2025 Hou, Wu, Li, Li, Yang, Chen, Zhou, Long, Wu, Fu, Guo and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yajie Guo, Department of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
Tong Wang, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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