Lipin1 as a therapeutic target for respiratory insufficiency of duchenne muscular dystrophy.

Autor:	Brown A; Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH, United States., Morris B; Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH, United States., Kamau JK; Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH, United States., Rakoczy RJ; Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH, United States., Finck BN; Division of Nutritional Science and Obesity Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, United States., Wyatt CN; Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH, United States., Ren H; Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2024 Nov 12; Vol. 15, pp. 1477976. Date of Electronic Publication: 2024 Nov 12 (Print Publication: 2024).
DOI:	10.3389/fphys.2024.1477976
Abstrakt:	In Duchenne muscular dystrophy (DMD), diaphragm muscle dysfunction results in respiratory insufficiency which is a leading cause of death in patients. Mutations to the dystrophin gene result in myocyte membrane instability, contributing to the structural deterioration of the diaphragm muscle tissues. With previous works suggesting the importance of lipin1 for maintaining skeletal muscle membrane integrity, we explored the roles of lipin1 in the dystrophic diaphragm. We found that the protein expression levels of lipin1 were reduced by 60% in the dystrophic diaphragm. While further knockdown of lipin1 in the dystrophic diaphragm leads to increased necroptosis, restoration of lipin1 in the dystrophic diaphragm results in reduced inflammation and fibrosis, decreased myofiber death, and improved respiratory function. Our results demonstrated that lipin1 restoration improved respiratory function by enhancing membrane integrity and suggested that lipin1 could be a potential therapeutic target for preventing respiratory insufficiency and respiratory failure in DMD. Continued investigation is required to better understand the mechanisms behind these findings, and to determine the role of lipin1 in maintaining muscle membrane stability. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Brown, Morris, Kamau, Rakoczy, Finck, Wyatt and Ren.)
Databáze:	MEDLINE
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