2. Academic Validation
  3. GATA-4 overexpressing BMSC-derived exosomes suppress H/R-induced cardiomyocyte ferroptosis

GATA-4 overexpressing BMSC-derived exosomes suppress H/R-induced cardiomyocyte ferroptosis

  • iScience. 2024 Aug 22;27(10):110784. doi: 10.1016/j.isci.2024.110784.
Zhiyuan Xiao 1,  Si Li 2,  Xinxin Wu 3,  Xinhao Chen 2,  Dan Yan 1,  Jigang He 4
Affiliations

Affiliations

  • 1 Department of Medical Intensive Care Unit, the First People's Hospital of Yunnan Province, No.157 Jinbi Road, Kunming, Yunnan 650032, China.
  • 2 The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650500, P.R. China.
  • 3 Yunnan University of Traditional Chinese Medicine, No.1076 Yuhua Road, Kunming, Yunnan 650500, China.
  • 4 Department of Cardiovascular Surgery, the First People's Hospital of Yunnan Province, No.157 Jinbi Road, Kunming, Yunnan 650032, China.
PMID: 39391723 DOI: 10.1016/j.isci.2024.110784
Abstract

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes overexpressing GATA-4 (Exosoe-GATA-4) can protect cardiac function. Mitochondrial permeability transition pore (mPTP) has a crucial role in Ferroptosis. This study aimed to assess the mechanism of Exosoe-GATA-4 in myocardial ischemia/reperfusion (I/R) injury. Exos were successfully excreted, and 185 differential expression miRNAs were obtained using bioinformatics. The Exosoe-GATA-4 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 Exosoe-GATA-4 on H/R-induced cardiomyocytes' Ferroptosis by downregulating SLC7A11. Mechanistically, BAP1 interacted with IP3R and increased cardiomyocytes' CA2+ level, causing mPTP opening and mitochondrial dysfunction, promoting H/R-induced cardiomyocytes' Ferroptosis. Moreover, hydrogen sulfide (H2S) content was increased and regulated the keap1/Nrf2 signaling pathway by Exosoe-GATA-4 treated. Exosoe-GATA-4 effectively suppresses H/R-induced cardiomyocytes' Ferroptosis by upregulating miR-330-3p, which regulates the BAP1/SLC7A11/IP3R axis and inhibits mPTP opening.

Keywords

Cell biology; Molecular biology.

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