AMPK Activation Regulates LTBP4-Dependent TGF-β1 Secretion by Pro-inflammatory Macrophages and Controls Fibrosis in Duchenne Muscular Dystrophy

Juban, Gaëtan; Saclier, Marielle; Yacoub‐Youssef, Houda; Kernou, Amel; Arnold, Ludovic; Boisson, Camille; Larbi, Sabrina Ben; Magnan, Mélanie; Cuvellier, Sylvain; Théret, Marine; Petrof, Basil J.; Desguerre, Isabelle; Gondin, Julien; Mounier, Rémi; Chazaud, Bénédicte

doi:10.1016/j.celrep.2018.10.077

Cited by 166 publications

(238 citation statements)

References 60 publications

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“…After a long debate on the origins of blood-derived MPs found in damaged tissue, it is now commonly accepted that infiltrating MPs (in contrast to tissue-resident MPs) only arise from Ly6C + MOs recruited from the bloodstream, and are associated with the scavenging of damaged tissue components, wound healing and tissue remodeling (Arnold et al, 2007;Mounier et al, 2013;Juban et al, 2018).…”

Section: Infiltrating Bone Marrow-derived Mpsmentioning

confidence: 99%

“…In this context, a clear role for inflammatory cells in modulating fibrosis has been shown. For example, whereas MPs act to clear stromal progenitors in the context of normal skeletal muscle regeneration, MPs found in chronically damaged muscle, despite being similar to early MPs in terms of surface phenotype, promote fibro/adipocytic progenitor survival and fibrogenic differentiation (Lemos et al, 2015;Juban et al, 2018). Interestingly, this phenotype may be reversed by treating mice with metformin, an activator of AMPK (an enzyme involved in MP-skewing following acute damage; Mounier et al, 2013).…”

Section: Skin and Hair Growth/repairmentioning

confidence: 99%

“…Indeed, in chronic disease, the asynchronous nature of the damage leads to contrasting signals being present within the muscle at the same time. This is likely to impair the functions of both myogenic and stromal progenitors, resulting in disrupted regeneration and fibrofatty infiltration (Dadgar et al, 2014;Tidball et al, 2014;Lemos et al, 2015;Tidball, 2017;Juban et al, 2018). In the future, a better understanding of MP functions and gene expression profiles in chronic disease is likely to lead to novel therapeutic approaches for chronic disease.…”

Section: Skin and Hair Growth/repairmentioning

confidence: 99%

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The origins and non-canonical functions of macrophages in development and regeneration

2019

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The discovery of new non-canonical (i.e. non-innate immune) functions of macrophages has been a recurring theme over the past 20 years. Indeed, it has emerged that macrophages can influence the development, homeostasis, maintenance and regeneration of many tissues and organs, including skeletal muscle, cardiac muscle, the brain and the liver, in part by acting directly on tissue-resident stem cells. In addition, macrophages play crucial roles in diseases such as obesity-associated diabetes or cancers. Increased knowledge of their regulatory roles within each tissue will therefore help us to better understand the full extent of their functions and could highlight new mechanisms modulating disease pathogenesis. In this Review, we discuss recent studies that have elucidated the developmental origins of various macrophage populations and summarize our knowledge of the non-canonical functions of macrophages in development, regeneration and tissue repair.

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Section: Infiltrating Bone Marrow-derived Mpsmentioning

confidence: 99%

Section: Skin and Hair Growth/repairmentioning

confidence: 99%

Section: Skin and Hair Growth/repairmentioning

confidence: 99%

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The origins and non-canonical functions of macrophages in development and regeneration

2019

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“…At the molecular level, the AMPK-SIRT1-PGC-1α axis plays a crucial role in mediating the diet-dependent increase of muscle regeneration. Consistently, pharmacological activation of AMPK by sir-tuin1, resveratrol, metformin, or AICAR was shown to mitigate the dystrophic phenotype in the mdx mouse model of DMD (Pauly et al, 2012;Ljubicic & Jasmin, 2015;Hafner et al, 2016;Juban et al, 2018). A fat-enriched diet regimen was also considered as a life-style strategy to revert the metabolic impairment of DMD.…”

Section: Introductionmentioning

confidence: 95%

Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration

et al. 2020

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In Duchenne muscular dystrophy (DMD), the absence of the dystrophin protein causes a variety of poorly understood secondary effects. Notably, muscle fibers of dystrophic individuals are characterized by mitochondrial dysfunctions, as revealed by a reduced ATP production rate and by defective oxidative phosphorylation. Here, we show that in a mouse model of DMD (mdx), fibro/adipogenic progenitors (FAPs) are characterized by a dysfunctional mitochondrial metabolism which correlates with increased adipogenic potential. Using high-sensitivity mass spectrometry–based proteomics, we report that a short-term high-fat diet (HFD) reprograms dystrophic FAP metabolism in vivo. By combining our proteomic dataset with a literature-derived signaling network, we revealed that HFD modulates the β-catenin–follistatin axis. These changes are accompanied by significant amelioration of the histological phenotype in dystrophic mice. Transplantation of purified FAPs from HFD-fed mice into the muscles of dystrophic recipients demonstrates that modulation of FAP metabolism can be functional to ameliorate the dystrophic phenotype. Our study supports metabolic reprogramming of muscle interstitial progenitor cells as a novel approach to alleviate some of the adverse outcomes of DMD.

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“…Consequently, muscle fibrosis develops which disrupts the cell niche for proper skeletal muscle regeneration (Murphy et al, 2011). Specifically, during chronic muscle damage, macrophage-derived TGF-β1, inhibits TNF-mediated FAP, and instead induce their fibrogenic differentiation and consequent extracellular matrix deposition (Lemos et al, 2015;Davies et al, 2016;Fiore et al, 2016;Juban et al, 2018). Similarly, Moratal et al (2018) report that IL-1β-activated macrophages and IL-4-polarized macrophages have opposite effects on FAP differentiation into adipocytes in vitro, which was dependent on Smad2 phosphorylation in FAPs.…”

Section: The Role Of Chronic Low-grade Inflammation In Metabolic Strementioning

confidence: 99%

Role of Metabolic Stress and Exercise in Regulating Fibro/Adipogenic Progenitors

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Farup

Lisio

2020

Front. Cell Dev. Biol.

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Obesity is a major public health concern and is associated with decreased muscle quality (i.e., strength, metabolism). Muscle from obese adults is characterized by increases in fatty, fibrotic tissue that decreases the force producing capacity of muscle and impairs glucose disposal. Fibro/adipogenic progenitors (FAPs) are muscle resident, multipotent stromal cells that are responsible for muscle fibro/fatty tissue accumulation. Additionally, they are indirectly involved in muscle adaptation through their promotion of myogenic (muscle-forming) satellite cell proliferation and differentiation. In conditions similar to obesity that are characterized by chronic muscle degeneration, FAP dysfunction has been shown to be responsible for increased fibro/fatty tissue accumulation in skeletal muscle, and impaired satellite cell function. The role of metabolic stress in regulating FAP differentiation and paracrine function in skeletal muscle is just beginning to be unraveled. Thus, the present review aims to summarize the recent literature on the role of metabolic stress in regulating FAP differentiation and paracrine function in skeletal muscle, and the mechanisms responsible for these effects. Furthermore, we will review the role of physical activity in reversing or ameliorating the detrimental effects of obesity on FAP function.

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AMPK Activation Regulates LTBP4-Dependent TGF-β1 Secretion by Pro-inflammatory Macrophages and Controls Fibrosis in Duchenne Muscular Dystrophy

Cited by 166 publications

References 60 publications

The origins and non-canonical functions of macrophages in development and regeneration

The origins and non-canonical functions of macrophages in development and regeneration

Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration

Role of Metabolic Stress and Exercise in Regulating Fibro/Adipogenic Progenitors

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