PPARγ Controls Ectopic Adipogenesis and Cross-Talks with Myogenesis During Skeletal Muscle Regeneration.
PPARγ Controls Ectopic Adipogenesis and Cross-Talks with Myogenesis During Skeletal Muscle Regeneration.
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DOI：
10.3390/ijms19072044
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发表时间：
2018-07-13
影响因子：
5.6
通讯作者：
Feige JN
中科院分区：
文献类型：
--
作者：
Dammone G;Karaz S;Lukjanenko L;Winkler C;Sizzano F;Jacot G;Migliavacca E;Palini A;Desvergne B;Gilardi F;Feige JN
骨骼肌是一种再生组织，可以通过激活组织驻留的肌肉干细胞（MuSC）来修复受损的肌纤维。许多再生受损的肌肉疾病导致肌肉中脂肪组织过度积累，改变MuSC的成肌命运，并解除MuSC和肌/脂肪生成祖细胞（FAP）之间的相互作用，FAP是一种支持肌生成并控制肌内纤维化和脂肪细胞形成的双能细胞群。为了更好地表征脂肪生成和肌生成之间的相互作用，我们研究了通过外胚层特异性Cre/lox缺失（PpargΔ/Δ）产生的全身Pparg null小鼠中的肌肉再生和MuSC功能。我们证明，PPARγ的缺失完全消除了再生过程中的异位肌肉脂肪生成，并损害了损伤后MuSC的扩增和肌生成。离体测定显示，PpargΔ/Δ小鼠中受干扰的肌生成主要不是由MuSC的内在缺陷或来自FAP的受干扰的肌生成支持引起的。再生期间从促炎性MuSC生态位到抗炎性MuSC生态位的免疫转变在PpargΔ/Δ小鼠中受到干扰，这表明巨噬细胞中的PPARγ信号传导可以与异位脂肪生成相互作用并影响肌肉再生。总之，我们的研究表明，PPARγ依赖性脂肪形成反应调节再生过程中的肌肉脂肪浸润，并且PPARγ是MuSC功能和有效肌肉修复所必需的。
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 (PpargΔ/Δ). We demonstrate that deletion of PPARγ completely abolishes ectopic muscle adipogenesis during regeneration and impairs MuSC expansion and myogenesis after injury. Ex vivo assays revealed that perturbed myogenesis in PpargΔ/Δ 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 PpargΔ/Δ mice and suggests that PPARγ signaling in macrophages can interact with ectopic adipogenesis and influence muscle regeneration. Altogether, our study demonstrates that a PPARγ-dependent adipogenic response regulates muscle fat infiltration during regeneration and that PPARγ is required for MuSC function and efficient muscle repair.
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影响因子：
20.1
作者：
Chawla A
通讯作者：
Chawla A
影响因子：
64.5
作者：
Festa E;Fretz J;Berry R;Schmidt B;Rodeheffer M;Horowitz M;Horsley V
通讯作者：
Horsley V
影响因子：
32.4
作者：
Kuswanto W;Burzyn D;Panduro M;Wang KK;Jang YC;Wagers AJ;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
64.5
作者：
Heredia JE;Mukundan L;Chen FM;Mueller AA;Deo RC;Locksley RM;Rando TA;Chawla A
通讯作者：
Chawla A
影响因子：
82.9
作者：
Hevener, AL;He, WM;Olefsky, J
通讯作者：
Olefsky, J