A muscle resident cell population promotes fibrosis in hindlimb skeletal muscles of mdx mice through the Wnt canonical pathway.
Previous work has pointed to a role for the Wnt canonical pathway in fibrosis formation in aged skeletal muscles. In the present study, we studied the dystrophic mdx mouse, which displays skeletal muscle fibrosis. Our results indicated that the muscle resident stromal cell (mrSC) population in the muscles of dystrophic mice is higher than in the muscles of age-matched wild-type mice. Wnt3a promoted the proliferation of and collagen expression by cultured mrSCs but arrested the growth of and collagen expression by cultured myoblasts. Injections of Wnt3A in the tibialis anterior muscles of adult wild-type mice significantly enhanced the mrSC population and collagen deposition compared with the contralateral muscles. Conversely, an injection of the Wnt antagonist Dickkof protein (DKK1) into the skeletal muscles of mdx mice significantly reduced collagen deposition. These results suggested that the Wnt canonical pathway expands the population of mrSCs and stimulates their production of collagen as observed during aging and in various myopathies.
Trensz
Frédéric
F
Research Center on Aging, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Haroun
Sonia
S
Cloutier
Alexandre
A
Richter
Martin V
MV
Grenier
Guillaume
G
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D049109:Cell Proliferation; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006614:Hindlimb / Q000033:anatomy & histology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D000950:Antigens, Ly; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D003094:Collagen