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

Varga, Tamas and Mounier, Remi and Patsalos, Andreas and Gogolák, Péter and Peloquin, Matthew and Nagy, Gergely and Póliska, Szilárd and Nagy, László (2016) Macrophage PPARg , a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration. IMMUNITY, 45. pp. 1038-1051. ISSN 1074-7613

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Abstract

Tissue regenerationrequiresinflammatoryand repar- atory activity of macrophages. Macrophages detect and eliminate the damaged tissue and subsequently promote regeneration. This dichotomy requires the switch of effector functions of macrophages coordi- nated 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, PPAR g , is required for proper skeletal muscle regeneration, acting in repair macrophages. PPAR g controls the expression of the transforming growth factor- b (TGF- b ) family member, GDF3, which in turn regu- lates the restoration of skeletal muscle integrity by promoting muscle progenitor cell fusion. This work establishes PPAR g 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 myo- blasts and serving as an exclusively macrophage- derived regeneration factor in tissue repair.

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