MEK-inhibitors decrease Nfix in muscular dystrophy but induce unexpected calcifications, partially rescued with Cyanidin diet
Articolo
Data di Pubblicazione:
2024
Citazione:
MEK-inhibitors decrease Nfix in muscular dystrophy but induce unexpected calcifications, partially rescued with Cyanidin diet / G. Angelini, E. Capra, F. Rossi, G. Mura, M. Saclier, V. Taglietti, G. Rovetta, R. Epis, G. Careccia, C. Bonfanti, G. Messina. - In: ISCIENCE. - ISSN 2589-0042. - 27:1(2024), pp. 108696.1-108696.20. [10.1016/j.isci.2023.108696]
Abstract:
Muscular dystrophies (MDs) are incurable genetic myopathies characterized by progressive degeneration
of skeletal muscles. Dystrophic mice lacking the transcription factor Nfix display morphological and func-
tional improvements of the disease. Recently, we demonstrated that MAPK signaling pathway positively
regulates Nfix in muscle development and that Cyanidin, a natural antioxidant molecule, strongly amelio-
rates the pathology. To explore a synergistic approach aimed at treating MDs, we administered Trameti-
nib, a clinically approved MEK inhibitor, alone or combined with Cyanidin to adult Sgca null mice. We
observed that chronic treatment with Trametinib and Cyanidin reduced Nfix in myogenic cells but, unex-
pectedly, caused ectopic calcifications exclusively in dystrophic muscles. The combined treatment with
Cyanidin resulted in histological improvements by preventing Trametinib-induced calcifications in Dia-
phragm and Soleus. Collectively, this first pilot study revealed that Nfix is modulated by the MAPK
pathway in MDs, and that Cyanidin partly rescued the unexpected ectopic calcifications caused by MEK
inhibition.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Cancer; Drugs; Pathophysiology
Elenco autori:
G. Angelini, E. Capra, F. Rossi, G. Mura, M. Saclier, V. Taglietti, G. Rovetta, R. Epis, G. Careccia, C. Bonfanti, G. Messina
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