GATA-4 Overexpressing BMSC-derived Exosomes Suppress H/R-induced Cardiomyocyte Ferroptosis

Overview

Journal iScience

Publisher Cell Press

Date 2024 Oct 11

PMID 39391723

Authors

Zhiyuan Xiao

Si Li

Xinxin Wu

Xinhao Chen

Dan Yan

Jigang He

Affiliations

Soon will be listed here.

Abstract

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes overexpressing GATA-4 (Exos) can protect cardiac function. Mitochondrial permeability transition pore (mPTP) has a crucial role in ferroptosis. This study aimed to assess the mechanism of Exos in myocardial ischemia/reperfusion (I/R) injury. Exos were successfully excreted, and 185 differential expression miRNAs were obtained using bioinformatics. The Exos effectively suppressed hypoxia/reoxygenation (H/R)-induced cardiomyocytes' ferroptosis, while the effects were reversed by miR-330-3p inhibitor. miR-330-3p targeted negative regulated BAP1. The effects of miR-330-3p inhibitor were reversed by knock-down BAP1. Also, BAP1 reversed the effects of Exos on H/R-induced cardiomyocytes' ferroptosis by downregulating SLC7A11. Mechanistically, BAP1 interacted with IP3R and increased cardiomyocytes' Ca level, causing mPTP opening and mitochondrial dysfunction, promoting H/R-induced cardiomyocytes' ferroptosis. Moreover, hydrogen sulfide (HS) content was increased and regulated the keap1/Nrf2 signaling pathway by Exos treated. Exos effectively suppresses H/R-induced cardiomyocytes' ferroptosis by upregulating miR-330-3p, which regulates the BAP1/SLC7A11/IP3R axis and inhibits mPTP opening.

Citing Articles

Mitochondrial Dysfunction in Cardiovascular Diseases.

Yang H Int J Mol Sci. 2025; 26(5).

PMID: 40076543 PMC: 11900462. DOI: 10.3390/ijms26051917.

The Potential of Mesenchymal Stem Cell-Derived Exosomes in Cardiac Repair.

Kundu D, Shin S, Chilian W, Dong F Int J Mol Sci. 2025; 25(24.

PMID: 39769256 PMC: 11727646. DOI: 10.3390/ijms252413494.

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