Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Resolvin D1 supports skeletal myofiber regeneration via actions on myeloid and muscle stem cells
James F. Markworth, … , Krishna Rao Maddipati, Susan V. Brooks
James F. Markworth, … , Krishna Rao Maddipati, Susan V. Brooks
Published August 4, 2020
Citation Information: JCI Insight. 2020;5(18):e137713. https://doi.org/10.1172/jci.insight.137713.
View: Text | PDF
Research Article Inflammation Muscle biology

Resolvin D1 supports skeletal myofiber regeneration via actions on myeloid and muscle stem cells

  • Text
  • PDF
Abstract

Specialized proresolving mediators (SPMs) actively limit inflammation and expedite its resolution by modulating leukocyte recruitment and function. Here we profiled intramuscular lipid mediators via liquid chromatography-tandem mass spectrometry–based metabolipidomics following myofiber injury and investigated the potential role of SPMs in skeletal muscle inflammation and repair. Both proinflammatory eicosanoids and SPMs increased following myofiber damage induced by either intramuscular injection of barium chloride or synergist ablation–induced functional muscle overload. Daily systemic administration of the SPM resolvin D1 (RvD1) as an immunoresolvent limited the degree and duration of inflammation, enhanced regenerating myofiber growth, and improved recovery of muscle strength. RvD1 suppressed inflammatory cytokine expression, enhanced polymorphonuclear cell clearance, modulated the local muscle stem cell response, and polarized intramuscular macrophages to a more proregenerative subset. RvD1 had minimal direct impact on in vitro myogenesis but directly suppressed myokine production and stimulated macrophage phagocytosis, showing that SPMs can modulate both infiltrating myeloid and resident muscle cell populations. These data reveal the efficacy of immunoresolvents as a novel alternative to classical antiinflammatory interventions in the management of muscle injuries to modulate inflammation while stimulating tissue repair.

Authors

James F. Markworth, Lemuel A. Brown, Eunice Lim, Carolyn Floyd, Jacqueline Larouche, Jesus A. Castor-Macias, Kristoffer B. Sugg, Dylan C. Sarver, Peter C.D. Macpherson, Carol Davis, Carlos A. Aguilar, Krishna Rao Maddipati, Susan V. Brooks

×

Figure 7

Resolvin D1 minimally affects the global transcriptomic response of muscle stem cells to injury but may modulate genes related to muscle-immune cell interactions.

Options: View larger image (or click on image) Download as PowerPoint
Resolvin D1 minimally affects the global transcriptomic response of musc...
C57BL/6 mice received bilateral intramuscular injection of the TA muscle with 50 μL of 1.2% BaCl2 induce myofiber injury. Mice were treated with daily IP injection with RvD1 (100 ng) or vehicle control (0.1% ethanol) for 72 hours. Both TA muscles were collected at day 3 postinjury and pooled. Muscle stem cells (satellite cells, MuSCs) were isolated by FACS, and transcriptome-wide profiling of the isolated MuSC population was performed by RNA-Seq. (A) Total MuSC yield from day 3 postinjury TA muscles. (B) Pooled mass of TA muscles used for MuSC isolation. (C) Relative MuSC yield. (D) Volcano plot of overall RNA-Seq data with each dot representing a single gene, positive log2 fold change (FC) indicating induction, and negative log2 FC indicating suppression in response to RvD1 treatment. Genes induced more than 2 FC (+1 log2 FC) are colored red, and those suppressed more than 2 FC (-1 log2 FC) are colored blue. (E) Gene ontology enrichment and respective FDRs for genes up- or downregulated more than 2 FC (irrespective of P value) in response to RvD1. Bars show the mean ± SEM of 3 mice per group with dots representing data from each mouse. P values were determined 2-tailed unpaired t tests (A–C) or limma-voom differential expression analysis (D).

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts