Data di Pubblicazione:
2012
Citazione:
Hmgb3 Is Regulated by MicroRNA-206 during Muscle Regeneration / S. Maciotta, M. Meregalli, L. Cassinelli, D. Parolini, A. Farini, G. Del Fraro, F. Gandolfi, M. Forcato, S. Ferrari, D. Gabellini, S. Bicciato, G. Cossu, Y. Torrente. - In: PLOS ONE. - ISSN 1932-6203. - 7:8(2012 Aug 17), pp. e43464.E43464.1-e43464.E43464.15. [10.1371/journal.pone.0043464]
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 39untranslated region (39UTR) 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
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S. Maciotta, M. Meregalli, L. Cassinelli, D. Parolini, A. Farini, G. Del Fraro, F. Gandolfi, M. Forcato, S. Ferrari, D. Gabellini, S. Bicciato, G. Cossu, Y. Torrente
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