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Publication : MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.

First Author  Wang H Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  8226
PubMed ID  39300060 Mgi Jnum  J:354659
Mgi Id  MGI:7732288 Doi  10.1038/s41467-024-52537-6
Citation  Wang H, et al. (2024) MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis. Nat Commun 15(1):8226
abstractText  Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C(-/-) mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.
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