Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis

Segawa, Masashi; Fukada, So‐ichiro; Yamamoto, Yoshiyuki; Yahagi, Hiroshi; Kanematsu, Masanori; Sato, Masaki; Ito, Takahito; Uezumi, Akiyoshi; Hayashi, S.; Miyagoe-Suzuki, Yuko; Takeda, Shin’ichi; Tsujikawa, Kazutake; Yamamoto, Hiroshi

doi:10.1016/j.yexcr.2008.08.008

Cited by 183 publications

(144 citation statements)

References 34 publications

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“…10 Blocking macrophage infiltration was found to delay SC proliferation and differentiation and to promote fibrosis. 11 Conversely, chronic inflammation accompanying severe myopathies are responsible for secondary damage promoting muscle degeneration and fibrosis. 12,13 Consequently, the intensity, duration and timeline of the inflammatory response as well as myeloid cell phenotype switches must strictly coordinate with tissue regeneration time-points for efficient repair.…”

Section: Resultsmentioning

confidence: 99%

Skeletal muscle regeneration involves macrophage-myoblast bonding

Ceafalan

Fertig

Popescu

et al. 2017

Cell Adhesion & Migration

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Regeneration in adult skeletal muscle relies on the activation, proliferation, and fusion of myogenic precursor cells (MPC), mostly resident satellite cells (SC). However, the regulatory mechanism during this process is still under evaluation, with the final aim to manipulate regeneration when the intrinsic mechanism is corrupted. Furthermore, intercellular connections during skeletal muscle regeneration have not been previously thoroughly documented. Our hypothesis was that a direct and close cellular interaction between SC/MPC and invading myeloid cells is a key step to control regeneration. We tested this hypothesis during different steps of skeletal muscle regeneration: (a) the recruitment of activated SC; (b) the differentiation of MPC; (c) myotubes growth, in a mouse model of crush injury. Samples harvested (3 and 5 days) post-injury were screened by light and confocal microscopy. Ultrastructural analysis was performed by conventional transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) followed by 3D modeling of electron tomography (ET) data. This revealed a new type of interaction between macrophages and myogenic cells by direct heterocellular surface apposition over large areas and long linear distances. In the analyzed volume, regions spaced below 20 nm, within molecular range, represented 31% of the macrophage membrane surface and more than 27% of the myotube membrane. The constant interaction throughout all stages of myogenesis suggests a potential new type of regulatory mechanism for the myogenic process. Thus, deciphering structural and molecular mechanisms of SC-macrophage interaction following injury might open promising perspectives for improving muscle healing.

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Section: Resultsmentioning

confidence: 99%

Skeletal muscle regeneration involves macrophage-myoblast bonding

Ceafalan

Fertig

Popescu

et al. 2017

Cell Adhesion & Migration

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“…6). This is pertinent because others report that treating macrophages with anti-M-CSF to inhibit macrophages of the M1 type causes defective muscle regeneration (20). Likewise, depletion of circulating monocytes in transgenic, CD11b diphtheria toxin receptor mice prevents muscle regeneration, including a reduction in the diameter of regenerating myofibers (21).…”

Section: Discussionmentioning

confidence: 99%

Role of Integrin-β3 Protein in Macrophage Polarization and Regeneration of Injured Muscle

Zhang

Dong

et al. 2012

Journal of Biological Chemistry

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Background: Integrin-␤3 is important for the cell migration and proliferation linked to muscle regeneration. Results: In mice with global integrin-␤3 KO, an initial macrophage polarization impairs muscle regeneration and stimulates fibrosis via TGF-␤1 production. Conclusion:In bone marrow cells, integrin-␤3 expression is necessary for macrophage-dependent processes of muscle repair. Significance: Stimulating integrin-␤3 could improve muscle regeneration.

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“…Macrophages are the best characterized inflammatory cells in the injured muscle (2,3), and in vivo studies have shown that they play an active role in the tissue repair process (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Macrophages dispose of apoptotic myofiber remnants and of debris, produce signals involved in matrix remodeling and neovessel formation, and regulate the activation, proliferation, and differentiation of muscle stem cells.…”

mentioning

confidence: 99%

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

Bosurgi

Corna

Vezzoli

et al. 2012

The Journal of Immunology

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The aim of this study was to verify whether macrophages influence the fate of transplanted mesoangioblasts—vessel-associated myogenic precursors—in a model of sterile toxin-induced skeletal muscle injury. We have observed that in the absence of macrophages, transplanted mesoangioblasts do not yield novel fibers. Macrophages retrieved from skeletal muscles at various times after injury display features that resemble those of immunoregulatory macrophages. Indeed, they secrete IL-10 and express CD206 and CD163 membrane receptors and high amounts of arginase I. We have reconstituted the muscle-associated macrophage population by injecting polarized macrophages before mesoangioblast injection: alternatively activated, immunoregulatory macrophages only support mesoangioblast survival and function. This action depends on the secretion of IL-10 in the tissue. Our results reveal an unanticipated role for tissue macrophages in mesoangioblast function. Consequently, the treatment of muscle disorders with mesoangioblasts should take into consideration coexisting inflammatory pathways, whose activation may prove crucial for its success.

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Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis

Cited by 183 publications

References 34 publications

Skeletal muscle regeneration involves macrophage-myoblast bonding

Skeletal muscle regeneration involves macrophage-myoblast bonding

Role of Integrin-β3 Protein in Macrophage Polarization and Regeneration of Injured Muscle

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

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