RGD Reference Report - Matrix metalloproteinase-9 inhibition improves proliferation and engraftment of myogenic cells in dystrophic muscle of mdx mice. - Rat Genome Database

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Matrix metalloproteinase-9 inhibition improves proliferation and engraftment of myogenic cells in dystrophic muscle of mdx mice.

Authors: Hindi, Sajedah M  Shin, Jonghyun  Ogura, Yuji  Li, Hong  Kumar, Ashok 
Citation: Hindi SM, etal., PLoS One. 2013 Aug 15;8(8):e72121. doi: 10.1371/journal.pone.0072121. eCollection 2013.
RGD ID: 13204809
Pubmed: PMID:23977226   (View Abstract at PubMed)
PMCID: PMC3744489   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0072121   (Journal Full-text)

Duchenne muscular dystrophy (DMD) caused by loss of cytoskeletal protein dystrophin is a devastating disorder of skeletal muscle. Primary deficiency of dystrophin leads to several secondary pathological changes including fiber degeneration and regeneration, extracellular matrix breakdown, inflammation, and fibrosis. Matrix metalloproteinases (MMPs) are a group of extracellular proteases that are involved in tissue remodeling, inflammation, and development of interstitial fibrosis in many disease states. We have recently reported that the inhibition of MMP-9 improves myopathy and augments myofiber regeneration in mdx mice (a mouse model of DMD). However, the mechanisms by which MMP-9 regulates disease progression in mdx mice remain less understood. In this report, we demonstrate that the inhibition of MMP-9 augments the proliferation of satellite cells in dystrophic muscle. MMP-9 inhibition also causes significant reduction in percentage of M1 macrophages with concomitant increase in the proportion of promyogenic M2 macrophages in mdx mice. Moreover, inhibition of MMP-9 increases the expression of Notch ligands and receptors, and Notch target genes in skeletal muscle of mdx mice. Furthermore, our results show that while MMP-9 inhibition augments the expression of components of canonical Wnt signaling, it reduces the expression of genes whose products are involved in activation of non-canonical Wnt signaling in mdx mice. Finally, the inhibition of MMP-9 was found to dramatically improve the engraftment of transplanted myoblasts in skeletal muscle of mdx mice. Collectively, our study suggests that the inhibition of MMP-9 is a promising approach to stimulate myofiber regeneration and improving engraftment of muscle progenitor cells in dystrophic muscle.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Duchenne muscular dystrophy treatmentISOMmp9 (Mus musculus)13204809; 13204809 RGD 
Duchenne muscular dystrophy treatmentIMP 13204809 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information