Angiopoietin-1 enhances skeletal muscle regeneration in mice

Abstract

Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang-1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle satellite cell survival; however, its role in skeletal muscle regeneration after injury is unknown. We assessed the effects of Ang-1 on fiber regeneration, myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA) in mice. We also assessed endogenous Ang-1 levels and localization in intact and injured TA muscles. TA fiber injury was triggered by cardiotoxin injection. Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin then increased during the 2 wk. Ang-1 protein was expressed in satellite cells, both in noninjured and recovering TA muscles. Positive Ang-1 staining was present in blood vessels but not in nerve fibers. Four days after the initiation of injury, injection of adenoviral Ang-1 into injured muscles resulted in significant increases in in situ TA muscle contractility, muscle fiber regeneration, and capillary density. In cultured human skeletal myoblasts, recombinant Ang-1 protein increased survival, proliferation, migration, and differentiation into myotubes. The latter effect was associated with significant upregulation of the expression of the myogenic regulatory factors MyoD and Myogenin and certain genes involved in cell cycle regulation. We conclude that Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angiogenesis program in endothelial cells.

The sea cucumber genome provides insights into morphological evolution and visceral regeneration

“…Many FREPs, like tenascin [49], fibrinogen-like protein [50], angiopoietin [51], and hepassocin [52], have been reported to be involved in the regulation of regeneration. These FREPs showed an obvious genome-wide gene duplication in A .…”

Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle

“…Although the importance of angiopoietin signaling in the vasculature is well defined, the cellular origins and functional roles of these two factors in skeletal muscle have only recently received attention. ANGPT1 is the principal angiopoietin produced by skeletal myoblasts and myotubes and is an important regulator of myogenesis and angiogenesis (38,42). Conversely, ANGPT2 has no effect on myoblast proliferation and migration and exerts a relatively weak and context-dependent effect on angiogenesis (41).…”

“…Conversely, ANGPT2 has no effect on myoblast proliferation and migration and exerts a relatively weak and context-dependent effect on angiogenesis (41). Mofarrahi et al (42) recently showed that overexpression of ANGPT1 following muscle injury in mice promoted capillary growth and accelerated the recovery of contractile performance. In this scenario, it is noteworthy that TH induced the expression of ANGPT1 in skeletal muscle (Fig.…”

BAG3 (Bcl-2–Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy

“…Although we saw efficient expression of our AAV in myofibers, we observed no immunofluorescence co-labeling of CD31 + , SMA + , and our FLAG-tagged construct, suggesting that our AAV6 serotype more efficiently infected and/or expressed in muscle cells in vivo . It is possible that improved muscle cell survival resulted in enhanced ischemia-induced expression of vascular growth factors and subsequent angiogenesis 65, 66 . Prior studies of murine HLI have supported the idea that pre-existing collateral vessels and arteriogenesis are critical determinants of necrosis and perfusion recovery 67, 68 .…”