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Hum Mol Genet. 2014 Jan 15;23(2):383-96. doi: 10.1093/hmg/ddt428. Epub 2013 Sep 5.

Laminin-111 improves muscle repair in a mouse model of merosin-deficient congenital muscular dystrophy.

Author information

1
Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557, USA and.

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.

PMID:
24009313
PMCID:
PMC3869356
DOI:
10.1093/hmg/ddt428
[Indexed for MEDLINE]
Free PMC Article

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