The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Physiol.
Sec. Striated Muscle Physiology
Volume 15 - 2024 |
doi: 10.3389/fphys.2024.1477976
Lipin1 as a Therapeutic Target for Respiratory Insufficiency of Duchenne Muscular Dystrophy
Provisionally accepted- 1 Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, United States
- 2 Department of Neuroscience, Cell Biology and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, United States
- 3 Division of Nutritional Science and Obesity Medicine, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
- 4 Boonshoft School of Medicine, Wright State University, Dayton, United States
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.
Keywords: Data curation, Formal analysis, methodology, Validation, visualization, Writing -review & editing. Brian Finck: Funding acquisition, resources, Writing -review & editing. Christopher N Wyatt: Resources
Received: 06 Sep 2024; Accepted: 28 Oct 2024.
Copyright: © 2024 Brown, Morris, Kamau, Rakoczy, Finck, Wyatt and Ren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hongmei Ren, Boonshoft School of Medicine, Wright State University, Dayton, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.