Aging‐associated genes and let‐7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy. Issue 6 (12th March 2019)

• Record Type: Journal Article
• Authors: Cappelletti, Cristina; Galbardi, Barbara; Bruttini, Mirella; Salerno, Franco; Canioni, Eleonora; Pasanisi, Maria Barbara; Rodolico, Carmelo; Brizzi, Teresa; Mora, Marina; Renieri, Alessandra; Maggi, Lorenzo; Bernasconi, Pia; Mantegazza, Renato
• Is Part Of: FASEB journal. Volume 33:Issue 6(2019)
• Page Start: 7155
• Page End: 7167
• Publication Date: 2019-03-12
• Subjects: differentiation -- regeneration -- skeletal muscle; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201801577RR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset muscle disease caused by an abnormal (GCN) triplet expansion within the polyadenylate‐binding protein nuclear 1 gene and consequent mRNA processing impairment and myogenic defects. Because a reduced cell proliferation potential and the consequent regeneration failure of aging muscle have been shown to be governed by lethal‐7 ( let‐7 ) microRNA‐mediated mechanisms, in the present study, we evaluated the role of let‐7 in the pathogenesis of OPMD. By a multidisciplinary approach, including conf ocal microscopy, Western blot, and quantitative PCR analyses on muscle biopsies from patients and unaffected individuals, we found a significant increase in let‐7 expression in OPMD muscles associated with an unusual high percentage of paired box 7–positive satellite cells. Furthermore, IL‐6, a cytokine involved in the regulation of satellite cell proliferation and differentiation and a potential target of let‐7, was found strongly down‐regulated in OPMD compared with control muscles. The decrease in IL‐6 transcript levels and protein content was also confirmed in vitro during differentiation of patients' and controls' muscle cells. Overall, our data suggest a key role of let‐7 in the regeneration and degeneration process in OPMD muscle and pointed to IL‐6 as a potential target molecule for new therapeutic approaches for this disorder.—Cappelletti, C., Galbardi, B., Bruttini, M., Salerno, F., Canioni, E., Pasanisi, M. B., Rodolico, C., Brizzi, T., Mora, M., Renieri, A., Maggi, L., Bernasconi, P., Mantegazza, R. Aging‐associated genes and let‐7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy. FASEB J. 33, 7155–7167 (2019). www.fasebj.org