Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury.

Autor:	Mohr ME; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.; These authors contributed equally., Li S; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.; These authors contributed equally., Trouten AM; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA., Stairley RA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA., Roddy PL; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA., Liu C; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Zhang M; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 200127 Shanghai, China., Sucov HM; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.; Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC 29425, USA., Tao G; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Feb 08. Date of Electronic Publication: 2023 Feb 08.
DOI:	10.1101/2023.02.07.527364
Abstrakt:	Neonatal mouse hearts have transient renewal capacity which is lost in juvenile and adult hearts. After myocardial infarction (MI) in neonatal hearts, an initial loss of cardiomyocytes occurs but it is unclear through which type of regulated cell death (RCD). In the current studies, we induced MI in neonatal and juvenile mouse hearts, and show that ischemic cardiomyocytes primarily undergo ferroptosis, a non-apoptotic and iron-dependent form of RCD. We demonstrate that cardiac fibroblasts (CFs) protect cardiomyocytes from ferroptosis through paracrine factors and direct cell-cell interaction. CFs show strong resistance to ferroptosis due to high ferritin expression. Meanwhile, the fibrogenic role of CFs, typically considered detrimental to heart function, is negatively regulated by paired-like homeodomain 2 (Pitx2) signaling from cardiomyocytes. In addition, Pitx2 prevents ferroptosis in cardiomyocytes by regulating ferroptotic genes. Understanding the regulatory mechanisms of cardiomyocyte survival and death can identify potentially translatable therapeutic strategies for MI. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
Databáze:	MEDLINE
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