Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice

Mozzetta, Chiara; Consalvi, Silvia; Saccone, Valentina; Tierney, Matthew; Diamantini, Adamo; Mitchell, Kathryn; Marazzi, Giovanna; Borsellino, Giovanna; Battistini, Luca; Sassoon, David; Sacco, Alessandra; Puri, Pier Lorenzo

doi:10.1002/emmm.201202096

Cited by 212 publications

(310 citation statements)

References 25 publications

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“…[50][51][52][53] Still a stage-dependent beneficial effect of HDACi treatment has been reported being HDACi efficacy restricted to early stages of the disease. 52,54 Interestingly, the refractoriness to HDACi treatment coincides with the premature block of autophagy reported in this work. Recent evidence underscores a role of HDACi in inducing autophagy 55,56 by directly regulating LC3 levels.…”

Section: Discussionsupporting

confidence: 81%

Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles

et al. 2016

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Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a 'disease modifier' targeted by interventions aimed to promote regeneration and delay disease progression in DMD.

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Section: Discussionsupporting

confidence: 81%

Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles

et al. 2016

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“…99 Intra-and intermuscular fat is a histopathological hallmark of persistently damaged 99 FAPs sustain satellite cell-driven myogenesis or directly differentiate into myoblasts in physiological conditions. 54 When regeneration fails because of satellite cell defect 55,100 and/or inadequate inflammatory response, 83 they generate adipocytes or differentiate into myofibroblasts. Myofibroblasts physiologically proliferate and synthesize extracellular matrix as scaffold to new fibers in reparative myogenesis.…”

Section: Outcomes Of Defective Apoptotic Cell Clearance: Maladaptivementioning

confidence: 99%

Cell death, clearance and immunity in the skeletal muscle

et al. 2016

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“…The isolation of satellite cells was performed as described [55]. Briefly, hind limb muscles were minced and digested in HBSS with CaCl 2 and MgCl 2 (Gibco) containing 2 lg/ml Collagenase A (Roche), 2.4 U/ml Dispase I (Roche), 10 ng/ml DNase I (Roche) for 120 min at 37°C.…”

Section: Isolation Of Satellite Cells By Facs From Brm Null and Wt Micementioning

confidence: 99%

Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis

et al. 2015

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Although the two catalytic subunits of the SWI/SNF chromatinremodeling complex-Brahma (Brm) and Brg1-are almost invariably co-expressed, their mutually exclusive incorporation into distinct SWI/SNF complexes predicts that Brg1-and Brm-based SWI/SNF complexes execute specific functions. Here, we show that Brg1 and Brm have distinct functions at discrete stages of muscle differentiation. While Brg1 is required for the activation of muscle gene transcription at early stages of differentiation, Brm is required for Ccnd1 repression and cell cycle arrest prior to the activation of muscle genes. Ccnd1 knockdown rescues the ability to exit the cell cycle in Brm-deficient myoblasts, but does not recover terminal differentiation, revealing a previously unrecognized role of Brm in the activation of late muscle gene expression independent from the control of cell cycle. Consistently, Brm null mice displayed impaired muscle regeneration after injury, with aberrant proliferation of satellite cells and delayed formation of new myofibers. These data reveal stage-specific roles of Brm during skeletal myogenesis, via formation of repressive and activatory SWI/SNF complexes.

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Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice

Cited by 212 publications

References 25 publications

Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles

Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles

Cell death, clearance and immunity in the skeletal muscle

Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis

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