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
“…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%
“…101 The counterpart of this event, that is, a self-perpetuating matrix deposition, eventually causing fibrosis, is characteristic of the persistently inflamed skeletal muscle. 56,[102][103][104] Heterotopic ossification may occur after severe traumatic skeletal muscle damage or neurological injury 105 and seems to result from inappropriate differentiation of mesenchymal progenitors. Persisting inflammation, inadequate phagocytosis and bone morphogenetic proteins activation are all thought to contribute.…”
Section: Outcomes Of Defective Apoptotic Cell Clearance: Maladaptivementioning
“…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%
“…101 The counterpart of this event, that is, a self-perpetuating matrix deposition, eventually causing fibrosis, is characteristic of the persistently inflamed skeletal muscle. 56,[102][103][104] Heterotopic ossification may occur after severe traumatic skeletal muscle damage or neurological injury 105 and seems to result from inappropriate differentiation of mesenchymal progenitors. Persisting inflammation, inadequate phagocytosis and bone morphogenetic proteins activation are all thought to contribute.…”
Section: Outcomes Of Defective Apoptotic Cell Clearance: Maladaptivementioning
“…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].…”
“…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
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