Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration

Tamas Varga, Rémi Mounier, Andreas Patsalos, Péter Gogolák, Matthew Peloquin, Attila Horvath, Attila Pap, Bence Daniel, Gergely Nagy, Eva Pintye, Szilárd Poliska, Sylvain Cuvellier, Sabrina Ben Larbi, Brian E. Sansbury, Matthew Spite, Chester W. Brown, Bénédicte Chazaud, Laszlo Nagy

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37 Citations (Scopus)

Abstract

Tissue regeneration requires inflammatory and reparatory activity of macrophages. Macrophages detect and eliminate the damaged tissue and subsequently promote regeneration. This dichotomy requires the switch of effector functions of macrophages coordinated with other cell types inside the injured tissue. The gene regulatory events supporting the sensory and effector functions of macrophages involved in tissue repair are not well understood. Here we show that the lipid activated transcription factor, PPARγ, is required for proper skeletal muscle regeneration, acting in repair macrophages. PPARγ controls the expression of the transforming growth factor-β (TGF-β) family member, GDF3, which in turn regulates the restoration of skeletal muscle integrity by promoting muscle progenitor cell fusion. This work establishes PPARγ as a required metabolic sensor and transcriptional regulator of repair macrophages. Moreover, this work also establishes GDF3 as a secreted extrinsic effector protein acting on myoblasts and serving as an exclusively macrophage-derived regeneration factor in tissue repair.

Original languageEnglish
Pages (from-to)1038-1051
Number of pages14
JournalImmunity
Volume45
Issue number5
DOIs
Publication statusPublished - Nov 15 2016

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Varga, T., Mounier, R., Patsalos, A., Gogolák, P., Peloquin, M., Horvath, A., Pap, A., Daniel, B., Nagy, G., Pintye, E., Poliska, S., Cuvellier, S., Ben Larbi, S., Sansbury, B. E., Spite, M., Brown, C. W., Chazaud, B., & Nagy, L. (2016). Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration. Immunity, 45(5), 1038-1051. https://doi.org/10.1016/j.immuni.2016.10.016