RT Journal Article
SR Electronic
T1 Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.19.517113
DO 10.1101/2022.11.19.517113
A1 Jesus A. Castor-Macias
A1 Jacqueline A. Larouche
A1 Emily C. Wallace
A1 Bonnie D. Spence
A1 Alec Eames
A1 Benjamin A. Yang
A1 Carol Davis
A1 Susan V. Brooks
A1 Krishna Rao Maddipati
A1 James F. Markworth
A1 Carlos A. Aguilar
YR 2022
UL http://biorxiv.org/content/early/2022/11/20/2022.11.19.517113.abstract
AB 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 improved myogenesis, leading to 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.Competing Interest StatementThe authors have declared no competing interest.