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Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury.

Publication ,  Journal Article
Blanc, RS; Kallenbach, JG; Bachman, JF; Mitchell, A; Paris, ND; Chakkalakal, JV
Published in: Nat Commun
August 20, 2020

Muscle regeneration depends on a robust albeit transient inflammatory response. Persistent inflammation is a feature of age-related regenerative deficits, yet the underlying mechanisms are poorly understood. Here, we find inflammatory-related CC-chemokine-receptor 2 (Ccr2) expression in non-hematopoietic myogenic progenitors (MPs) during regeneration. After injury, the expression of Ccr2 in MPs corresponds to the levels of its ligands, the chemokines Ccl2, 7, and 8. We find stimulation of Ccr2-activity inhibits MP fusion and contribution to myofibers. This occurs in association with increases in MAPKp38δ/γ signaling, MyoD phosphorylation, and repression of the terminal myogenic commitment factor Myogenin. High levels of Ccr2-chemokines are a feature of regenerating aged muscle. Correspondingly, deletion of Ccr2 in MPs is necessary for proper fusion into regenerating aged muscle. Finally, opportune Ccr2 inhibition after injury enhances aged regeneration and functional recovery. These results demonstrate that inflammatory-induced activation of Ccr2 signaling in myogenic cells contributes to aged muscle regenerative decline.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 20, 2020

Volume

11

Issue

1

Start / End Page

4167

Location

England

Related Subject Headings

  • Wounds and Injuries
  • Signal Transduction
  • Satellite Cells, Skeletal Muscle
  • Regeneration
  • Receptors, CCR2
  • Myogenin
  • Muscle, Skeletal
  • Muscle Development
  • Mice, Knockout
  • Mice, Inbred C57BL
 

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Blanc, R. S., Kallenbach, J. G., Bachman, J. F., Mitchell, A., Paris, N. D., & Chakkalakal, J. V. (2020). Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury. Nat Commun, 11(1), 4167. https://doi.org/10.1038/s41467-020-17620-8
Blanc, Roméo S., Jacob G. Kallenbach, John F. Bachman, Amanda Mitchell, Nicole D. Paris, and Joe V. Chakkalakal. “Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury.Nat Commun 11, no. 1 (August 20, 2020): 4167. https://doi.org/10.1038/s41467-020-17620-8.
Blanc RS, Kallenbach JG, Bachman JF, Mitchell A, Paris ND, Chakkalakal JV. Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury. Nat Commun. 2020 Aug 20;11(1):4167.
Blanc, Roméo S., et al. “Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury.Nat Commun, vol. 11, no. 1, Aug. 2020, p. 4167. Pubmed, doi:10.1038/s41467-020-17620-8.
Blanc RS, Kallenbach JG, Bachman JF, Mitchell A, Paris ND, Chakkalakal JV. Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury. Nat Commun. 2020 Aug 20;11(1):4167.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 20, 2020

Volume

11

Issue

1

Start / End Page

4167

Location

England

Related Subject Headings

  • Wounds and Injuries
  • Signal Transduction
  • Satellite Cells, Skeletal Muscle
  • Regeneration
  • Receptors, CCR2
  • Myogenin
  • Muscle, Skeletal
  • Muscle Development
  • Mice, Knockout
  • Mice, Inbred C57BL