Angiopoietin‐1 Enhances Skeletal Muscle Regeneration in Mice

Abstract

Activation of muscle progenitor cell myogenesis and endothelial cell (EC) angiogenesis (angio‐) is critical for the recovery of skeletal muscle (SM) from injury. Angiopoietin‐1 (Ang‐1) enhances angio‐ and SM satellite cell survival; however, its role in SM regeneration after injury is unknown. We assessed the effects of Ang‐1 on fiber regeneration (FR), myogenesis, and angio‐ in injured SM (tibialis anterior, TA) in mice.TA fiber injury was triggered by cardiotoxin (CTX). Endogenous Ang‐1 mRNA levels immediately decreased in response to CTX then increased over the course of two weeks. Ang‐1 protein was expressed in satellite cells, both in non‐injured and recovering TA. Four days after the initiation of injury, injection of adenoviral Ang‐1 into injured muscles resulted in significant increases in in situ TA contractility, muscle FR, and capillary density. In cultured human skeletal myoblasts, recombinant Ang‐1 protein increased survival, proliferation, migration, and differentiation into myotubes. We conclude that Ang‐1 strongly enhances SM regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angio‐ program in EC.