The microRNA miR-133b functions to slow Duchenne muscular dystrophy pathogenesis.

Autor: Taetzsch T; Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA., Shapiro D; Molecular Biology, Cell Biology, & Biochemistry Graduate Program, Brown University, Providence, RI, USA., Eldosougi R; Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA., Myers T; Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA., Settlage RE; Advanced Research Computing, Virginia Tech, Blacksburg, VA, USA., Valdez G; Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.; Center for Translational Neuroscience, Robert J. and Nancy D. Carney Institute for Brain Science and Brown Institute for Translational Science, Brown University, Providence, United States.; Department of Neurology, Warren Alpert Medical School of Brown University, Providence, United States.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2021 Jan; Vol. 599 (1), pp. 171-192. Date of Electronic Publication: 2020 Oct 24.
DOI: 10.1113/JP280405
Abstrakt: Key Points: Impairment of muscle biogenesis contributes to the progression of Duchenne muscular dystrophy (DMD). As a muscle enriched microRNA that has been implicated in muscle biogenesis, the role of miR-133b in DMD remains unknown. To assess miR-133b function in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. We show that deletion of miR-133b exacerbates the dystrophic phenotype of DMD-afflicted skeletal muscle by dysregulating muscle stem cells involved in muscle biogenesis, in addition to affecting signalling pathways related to inflammation and fibrosis. Our results provide evidence that miR-133b may underlie DMD pathology by affecting the proliferation and differentiation of muscle stem cells.
Abstract: Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle degeneration. No treatments are currently available to prevent the disease. While the muscle enriched microRNA miR-133b has been implicated in muscle biogenesis, its role in DMD remains unknown. To assess miR-133b function in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of P30 mdx mice is smaller in size and exhibits a thickened interstitial space containing more mononucleated cells. Additional analysis revealed that miR-133b deletion influences muscle fibre regeneration, satellite cell proliferation and differentiation, and induces widespread transcriptomic changes in mdx muscle. These include known miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.
(© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)
Databáze: MEDLINE
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