Maresin 1 repletion improves muscle regeneration after volumetric muscle loss
- University of Michigan-Ann Arbor, United States
- Wayne State University, United States
- Purdue University West Lafayette, United States
Abstract
The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE215808
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Maresin 1 repletion improves muscle regeneration after volumetric muscle lossNCBI Gene Expression Omnibus, GSE215808.
Article and author information
Author details
Jacqueline A Larouche
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30 AR069620)
- Carlos A Aguilar
Congressionally Directed Medical Research Programs (W81XWH2010336)
- Carlos A Aguilar
Congressionally Directed Medical Research Programs (W81XWH2110491)
- Carlos A Aguilar
3M Foundation
- Carlos A Aguilar
American Federation for Aging Research
- Carlos A Aguilar
National Science Foundation (2045977)
- Carlos A Aguilar
Defense Advanced Research Projects Agency (D20AC0002)
- Carlos A Aguilar
Hevolution Foundation
- Carlos A Aguilar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christopher L-H Huang, University of Cambridge, United Kingdom
Ethics
Animal experimentation: All mice were fed normal chow ad libitum and housed on a 12:12 hour light-dark cycle under UM veterinary staff supervision. Allprocedures were approved by the Institutional Animal Care and Use Committee (IACUC) andwere in accordance with the U.S. National Institute of Health (NIH).
Version history
- Preprint posted: November 20, 2022 (view preprint)
- Received: January 26, 2023
- Accepted: December 21, 2023
- Accepted Manuscript published: December 22, 2023 (version 1)
- Version of Record published: January 24, 2024 (version 2)
Copyright
© 2023, Castor-Macias et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Maresin 1 repletion improves muscle regeneration after volumetric muscle loss
eLife 12:e86437.
https://doi.org/10.7554/eLife.86437
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