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Publication : PPARĪ³ Controls Ectopic Adipogenesis and Cross-Talks with Myogenesis During Skeletal Muscle Regeneration.

First Author  Dammone G Year  2018
Journal  Int J Mol Sci Volume  19
Issue  7 PubMed ID  30011852
Mgi Jnum  J:289731 Mgi Id  MGI:6434638
Doi  10.3390/ijms19072044 Citation  Dammone G, et al. (2018) PPARgamma Controls Ectopic Adipogenesis and Cross-Talks with Myogenesis During Skeletal Muscle Regeneration. Int J Mol Sci 19(7):2044
abstractText  Skeletal muscle is a regenerative tissue which can repair damaged myofibers through the activation of tissue-resident muscle stem cells (MuSCs). Many muscle diseases with impaired regeneration cause excessive adipose tissue accumulation in muscle, alter the myogenic fate of MuSCs, and deregulate the cross-talk between MuSCs and fibro/adipogenic progenitors (FAPs), a bi-potent cell population which supports myogenesis and controls intra-muscular fibrosis and adipocyte formation. In order to better characterize the interaction between adipogenesis and myogenesis, we studied muscle regeneration and MuSC function in whole body Pparg null mice generated by epiblast-specific Cre/lox deletion (Pparg(Delta/Delta)). We demonstrate that deletion of PPARgamma completely abolishes ectopic muscle adipogenesis during regeneration and impairs MuSC expansion and myogenesis after injury. Ex vivo assays revealed that perturbed myogenesis in Pparg(Delta/Delta) mice does not primarily result from intrinsic defects of MuSCs or from perturbed myogenic support from FAPs. The immune transition from a pro- to anti-inflammatory MuSC niche during regeneration is perturbed in Pparg(Delta/Delta) mice and suggests that PPARgamma signaling in macrophages can interact with ectopic adipogenesis and influence muscle regeneration. Altogether, our study demonstrates that a PPARgamma-dependent adipogenic response regulates muscle fat infiltration during regeneration and that PPARgamma is required for MuSC function and efficient muscle repair.
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