1α,25(OH)2-vitamin D3 increases dysferlin expression in vitro and in a human clinical trial
Luna, Noemí de (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Diaz-Manera, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Paradas, Carmen (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Iturriaga, Cristina (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Rojas-Garcia, Ricardo (Institut d'Investigació Biomèdica Sant Pau)
Araque, Josefa (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Genebriera, Mireia (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Gich, Ignasi (Institut d'Investigació Biomèdica Sant Pau)
Illa, Isabel (Institut d'Investigació Biomèdica Sant Pau)
Gallardo, Eduard (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2012
Abstract:	Dysferlinopathies are a heterogenous group of autosomal recessive inherited muscular dystrophies caused by mutations in DYSF gene. Dysferlin is expressed mainly in skeletal muscle and in monocytes and patients display a severe reduction or absence of protein in both tissues. Vitamin D3 promotes differentiation of the promyelocytic leukemia HL60 cells. We analyzed the effect of vitamin D3 on dysferlin expression in vitro using HL60 cells, monocytes and myotubes from controls and carriers of a single mutation in DYSF. We also performed an observational study with oral vitamin D3 in a cohort of 21 carriers. Fifteen subjects were treated for 1 year and dysferlin expression in monocytes was analysed before and after treatment. Treatment with vitamin D3 increased expression of dysferlin in vitro. The effect of vitamin D3 was mediated by both a nongenomic pathway through MEK/ERK and a genomic pathway involving binding of vitamin D3 receptor to the dysferlin promoter. Carriers treated with vitamin D3 had significantly increased expression of dysferlin in monocytes compared with nontreated carriers (P 0. 05). These findings will have important therapeutic implications since a combination of different molecular strategies together with vitamin D3 uptake could increase dysferlin expression to nonpathological protein levels. © The American Society of Gene & Cell Therapy.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-1004 Ministerio de Ciencia e Innovación 08/90622
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Molecular Therapy, Vol. 20 Núm. 10 (october 2012) , p. 1988-1997, ISSN 1525-0024

DOI: 10.1038/mt.2012.156
PMID: 22910291

10 p, 1012.8 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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