title: Therapeutic effects of exon skipping and losartan on skeletal muscle of mdx mice.
abstract: Various attempts have been made to find treatments for Duchenne muscular dystrophy (DMD) patients. Exon skipping is one of the promising technologies for DMD treatment by restoring dystropin protein, which is one of the muscle components. It is well known that losartan, an angiotensin II type1 receptor blocker, promotes muscle regeneration and differentiation by lowering the level of transforming growth factor-beta1 signaling. In this study, we illustrated the combined effects of exon skipping and losartan on skeletal muscle of mdx mice. We supplied mdx mice with losartan for 2 weeks before exon skipping treatment. The losartan with the exon skipping group showed less expression of myf5 than the losartan treated group. Also the losartan with exon skipping group recovered normal muscle architecture, in contrast to the losartan group which still showed many central nuclei. However, the exon skipping efficiency and the restoration of dystrophin protein were lower in the losartan with exon skipping group compared to the exon skipping group. We reveal that losartan promotes muscle regeneration and shortens the time taken to restore normal muscle structure when combined with exon skipping. However, combined treatment of exon skipping and losartan decreases the restoration of dystrophin protein meaning decrease of exon skipping efficiency.
authors.affiliation: College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea; Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Lee
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Myeong-Mi
authors.initials: MM
authors.lastname: Lee
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Min
authors.forename: Kyung-Ku
authors.initials: KK
authors.lastname: Kang
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Meeyul
authors.initials: M
authors.lastname: Hwang
authors.forename: Soon-Hak
authors.initials: SH
authors.lastname: Kwon
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000378:metabolism; D005091:Exons / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000473:pathology
chemical_list: D016189:Dystrophin; D019808:Losartan
keywords: combined effect; exon skipping; losartan; mdx mice; muscle regeneration