Hmgb3 is regulated by microRNA-206 during muscle regeneration

Simona Maciotta, Mirella Meregalli, Letizia Cassinelli, Daniele Parolini, Andrea Farini, Giulia Del Fraro, Francesco Gandolfi, Mattia Forcato, Sergio Ferrari, Davide Gabellini, Silvio Bicciato, Giulio Cossu, Yvan Torrente

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background: MicroRNAs (miRNAs) have been recently involved in most of human diseases as targets for potential strategies to rescue the pathological phenotype. Since the skeletal muscle is a spread-wide highly differentiated and organized tissue, rescue of severely compromised muscle still remains distant from nowadays. For this reason, we aimed to identify a subset of miRNAs major involved in muscle remodelling and regeneration by analysing the miRNA-profile of single fibres isolated from dystrophic muscle, which was here considered as a model of chronic damage. Methodology/Principal Findings: The miRNA-signature associated to regenerating (newly formed) and remodelling (resting) fibres was investigated in animal models of muscular dystrophies and acute damage, in order to distinguish which miRNAs are primary related to muscle regeneration. In this study we identify fourteen miRNAs associated to dystrophic fibres responsible for muscle regeneration and remodelling, and confirm over-expression of the previously identified regeneration-associated myomiR-206. In particular, a functional binding site for myomiR-206 was identified and validated in the 3′untranslated region (3′UTR) of an X-linked member of a family of sequence independent chromatin-binding proteins (Hmgb3) that is preferentially expressed in hematopoietic stem cells. During regeneration of single muscle fibres, Hmgb3 messenger RNA (mRNA) and protein expression was gradually reduced, concurrent with the up-regulation of miR-206. Conclusion/Significance: Our results elucidate a negative feedback circuit in which myomiR-206 represses Hmgb3 expression to modulate the regeneration of single muscle fibres after acute and chronic muscle damage. These findings suggest that myomiR-206 may be a potential therapeutic target in muscle diseases. © 2012 Maciotta et al.
    Original languageEnglish
    Article numbere43464
    JournalPLoS ONE
    Volume7
    Issue number8
    DOIs
    Publication statusPublished - 17 Aug 2012

    Fingerprint

    Dive into the research topics of 'Hmgb3 is regulated by microRNA-206 during muscle regeneration'. Together they form a unique fingerprint.

    Cite this