Inhibition of microRNA-92a increases blood vessels and satellite cells in skeletal muscle but does not improve duchenne muscular dystrophy-related phenotype in mdx mice.

INTRODUCTION

The vasculature and blood flow in muscle are perturbed in Duchenne muscular dystrophy (DMD) and its mdx mouse model. MicroRNA-92a (miR-92a) is enriched in endothelial cells, especially during ischemic injury.

METHODS

Because antagonizing miR-92a was shown to result in increased proliferation and migration of endothelial cells and recovery from ischemia, we assessed the effects of Antagomir-92a in vitro in muscle stem cell culture and in vivo in mdx mice.

RESULTS

miR-92a was found to be highly expressed in muscle endothelial cells and satellite cells. Treatment with Antagomir-92a increased capillary density and tissue perfusion, which was accompanied by an increase in satellite cells. However, Antagomir-92a-treated mdx mice showed no histological improvement and had worse muscle function. Antagomir-92a suppressed myogenic differentiation in satellite cell culture.

DISCUSSION: AntagomiR-92a improves the vasculature but not the muscle in mdx mice, possibly due to its side effects on satellite cell differentiation. Muscle Nerve 59:594-594, 2019.