2015
DOI: 10.1038/nm.3869
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Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors

Abstract: Depending on the inflammatory milieu, injury can result either in a tissue's complete regeneration or in its degeneration and fibrosis, the latter of which could potentially lead to permanent organ failure. Yet how inflammatory cells regulate matrix-producing cells involved in the reparative process is unknown. Here we show that in acutely damaged skeletal muscle, sequential interactions between multipotent mesenchymal progenitors and infiltrating inflammatory cells determine the outcome of the reparative proc… Show more

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Cited by 577 publications
(898 citation statements)
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“…Defective FAP clearance reflects and contributes to the maladaptive remodeling of the skeletal muscle. 56 Inflammatory leukocytes represent another source of dying cells in the damaged/regenerating skeletal muscle. Their fate has not been characterized in detail.…”
Section: Unique Immune Privileges Of the Skeletal Musclementioning
confidence: 99%
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“…Defective FAP clearance reflects and contributes to the maladaptive remodeling of the skeletal muscle. 56 Inflammatory leukocytes represent another source of dying cells in the damaged/regenerating skeletal muscle. Their fate has not been characterized in detail.…”
Section: Unique Immune Privileges Of the Skeletal Musclementioning
confidence: 99%
“…76 In contrast, other crucial pathways, such as those coordinated by myeloid hypoxia-inducible factors, are apparently dispensable for M1/M2 shift and muscle healing after sterile injury. 82 Of importance, other cells, including eosinophils and FAPs, are apparently involved in the clearance of necrotic muscle debris in experimental models 56,83 (Figure 2). Even myoblasts in vitro appear to be endowed with the ability to internalize apoptotic myoblasts.…”
Section: The Predators: Macrophages Scavenge Muscle Debrismentioning
confidence: 99%
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“…Cette présence prolongée des macrophages pro-inflammatoires est à l'origine des effets myotoxiques [24]. De plus, dans les muscles de souris dystrophiques mdx, les macrophages présentent un phé-notype hybride et sécrètent du TGF-β qui agit sur les progéniteurs fibro-adipogéniques (FAP) et stimule la fibrose (Figure 3) [35]. Les lymphocytes sont eux aussi impliqués dans la dégénérescence des muscles dystrophiques [30].…”
Section: Vieillissementunclassified
“…fibro-adipogenic progenitors -FAPs) and MuSCs appear a key determinant to drive the skeletal muscle toward a regeneration or degeneration process. [6,7] This notion has inspired a number of current pharmacological strategies aimed at targeting these cells and the functional networks they establish, [8,9] as an alternative to gene replacement and cell-based strategies.…”
Section: Hdac Inhibitors For Muscular Dystrophies: Progress and Prospmentioning
confidence: 99%