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Updated: Mar 24, 2026
Immunolabelling Myofiber Degeneration in Muscle Biopsies
Published on: December 5, 2019
Muscle-specific microRNAs as biomarkers of Duchenne Muscular Dystrophy progression and response to therapies
L Giordani1, M Sandoná2, A Rotini2
1Sanford-Burnham Medical Research Institute; Sanford Children's Health; Research Center , La Jolla, CA USA.
Abstract:
Recent studies have revealed the contribution of fibro-adipogenic progenitors (FAPs) to the pathogenesis and progression of Duchenne Muscular Dystrophy (DMD). While FAPs direct compensatory regeneration at early stages of disease, as the disease progresses they contribute to the progressive replacement of contractile myofibers with fibrotic scars and fatty infiltration. Using the mouse model of DMD - the mdx mice - we have recently reported that FAPs mediate the ability of HDAC inhibitors (HDACi) to promote muscle regeneration and prevent fibro-adipogenic degeneration at early stages of disease. This effect is mediated by the induction of myomiRs that, in turn, target the SWI/SNF components BAF60A and B, thereby favoring the formation of BAF60C-based SWI/SNF complex, which directs the switch from the fibro-adipogenic to the myogenic lineage. Here we show direct evidence of induction of miR-206 and BAF60C, and reduction of BAF60A, in FAPs isolated from mdx muscles exposed to the HDACi Trichostatin A (TSA). We also discuss how increased expression of myomiRs in dystrophic muscles can be integrated with circulating myomiRs to provide accurate biomarkers of disease progression and response to treatment.
Insights
Fibro-adipogenic progenitors (FAPs) contribute to Duchenne Muscular Dystrophy (DMD) progression. HDAC inhibitors promote muscle regeneration by shifting FAPs from a fibro-adipogenic to a myogenic lineage via myomiRs.
Area of Science:
- Muscle biology
- Cellular and molecular medicine
- Biomarkers
Background:
- Fibro-adipogenic progenitors (FAPs) play a dual role in Duchenne Muscular Dystrophy (DMD), promoting regeneration early on but driving fibrosis and fat infiltration later.
- HDAC inhibitors (HDACi) have shown potential in early-stage DMD treatment by modulating FAP behavior.
Purpose of the Study:
- To investigate the mechanism by which HDAC inhibitors (HDACi) influence fibro-adipogenic progenitors (FAPs) in the context of Duchenne Muscular Dystrophy (DMD).
- To explore the role of myomiRs and SWI/SNF complexes in mediating the therapeutic effects of HDACi on FAPs.
Main Methods:
- Isolation of FAPs from mdx mouse muscles (a model for DMD).
- Treatment of isolated FAPs with Trichostatin A (TSA), a histone deacetylase inhibitor (HDACi).
- Analysis of gene and microRNA expression, focusing on myomiRs and SWI/SNF components.
Main Results:
- Trichostatin A (TSA) induced miR-206 and BAF60C expression while reducing BAF60A in FAPs from mdx mice.
- HDAC inhibition promotes a shift in FAPs towards a myogenic lineage by altering SWI/SNF complex composition.
- MyomiRs are key mediators of HDACi's beneficial effects on FAPs in DMD.
Conclusions:
- HDAC inhibitors, through myomiR induction, can reprogram FAPs to promote muscle regeneration and counteract fibro-adipogenic degeneration in DMD.
- MyomiR expression patterns in dystrophic muscles and circulation may serve as valuable biomarkers for DMD progression and treatment efficacy.
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