Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles

Flavia A. Graca, Anna Stephan, Benjamin A. Minden-Birkenmaier, Abbas Shirinifard, Yong-Dong Wang, Fabio Demontis () and Myriam Labelle ()
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Flavia A. Graca: St. Jude Children’s Research Hospital
Anna Stephan: St. Jude Children’s Research Hospital
Benjamin A. Minden-Birkenmaier: St. Jude Children’s Research Hospital
Abbas Shirinifard: St. Jude Children’s Research Hospital
Yong-Dong Wang: St. Jude Children’s Research Hospital
Fabio Demontis: St. Jude Children’s Research Hospital
Myriam Labelle: St. Jude Children’s Research Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to muscle repair but whether platelets promote regeneration beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines is an early event necessary for muscle repair in mice. Platelet depletion reduces the levels of the platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase neutrophil infiltration to injured muscles is impaired whereas later inflammation is exacerbated. Consistent with this model, neutrophil infiltration to injured muscles is compromised in male mice with Cxcl7-knockout platelets. Moreover, neo-angiogenesis and the re-establishment of myofiber size and muscle strength occurs optimally in control mice post-injury but not in Cxcl7ko mice and in neutrophil-depleted mice. Altogether, these findings indicate that platelet-secreted CXCL7 promotes regeneration by recruiting neutrophils to injured muscles, and that this signaling axis could be utilized therapeutically to boost muscle regeneration.

Date: 2023
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DOI: 10.1038/s41467-023-38624-0

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