Maresin 1 repletion improves muscle regeneration after volumetric muscle loss

Abstract
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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

The following data sets were generated

1. Aguilar CA
2. et al
(2023) Maresin 1 repletion improves muscle regeneration after volumetric muscle loss
NCBI Gene Expression Omnibus, GSE215808.

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215808

Article and author information

Author details

Jesus A Castor-Macias

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Jacqueline A Larouche

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9380-3547
Emily C Wallace

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Bonnie D Spence

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Alec Eames

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Pamela Duran

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Benjamin A Yang

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Paula M Fraczek

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Carol A Davis

Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Susan V Brooks

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Krishna Rao Maddipati

Department of Pathology, Wayne State University, Detroit, United States

Competing interests
The authors declare that no competing interests exist.
James F Markworth

Department of Animal Sciences, Purdue University West Lafayette, West Lafayette, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5348-1464
Carlos A Aguilar

Department of Biomedical Engineering, University of Michigan-Ann Arbor, Ann Arbor, United States

For correspondence
caguilar@umich.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3830-0634

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.

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).

Copyright

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.