title: Laminin-111 improves muscle repair in a mouse model of merosin-deficient congenital muscular dystrophy.
abstract: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a severe and fatal muscle-wasting disease with no cure. MDC1A patients and the dy(W-/-) mouse model exhibit severe muscle weakness, demyelinating neuropathy, failed muscle regeneration and premature death. We have recently shown that laminin-111, a form of laminin found in embryonic skeletal muscle, can substitute for the loss of laminin-211/221 and prevent muscle disease progression in the dy(W-/-) mouse model. What is unclear from these studies is whether laminin-111 can restore failed regeneration to laminin-α2-deficient muscle. To investigate the potential of laminin-111 protein therapy to improve muscle regeneration, laminin-111 or phosphate-buffered saline-treated laminin-α2-deficient muscle was damaged with cardiotoxin and muscle regeneration quantified. Our results show laminin-111 treatment promoted an increase in myofiber size and number, and an increased expression of α7β1 integrin, Pax7, myogenin and embryonic myosin heavy chain, indicating a restoration of the muscle regenerative program. Together, our results show laminin-111 restores muscle regeneration to laminin-α2-deficient muscle and further supports laminin-111 protein as a therapy for the treatment of MDC1A.
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557, USA and.
authors.forename: Pam M
authors.initials: PM
authors.lastname: Van Ry
authors.forename: Priscilla
authors.initials: P
authors.lastname: Minogue
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Hodges
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Burkin
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000188:drug therapy; D005786:Gene Expression Regulation; D007797:Laminin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000188:drug therapy* / Q000473:pathology*; D009137:Muscular Dystrophy, Animal; D018008:Myogenin / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism
chemical_list: D007797:Laminin; D018008:Myogenin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse