Angiotensin II signalling regulates skeletal muscle growth and myoblast chemotaxis

The regulatory role of angiotensin II (Ang II) in mediating skeletal muscle hypertrophy is largely unknown. We examined the impact of Ang II on myoblast chemotaxis using transwell assays. Exogenous treatment of Ang II significantly increased the migratory capacity of both C2C12 and primary myoblasts by 30 and 43% respectively, while Ang II receptor knockout myoblasts (AT1a −/− ) demonstrated a significant attenuation of basal migration (38% of control) and did not respond to exogenous Ang II treatment. Ang II appeared to increase migration by inducing MMP2 activity as gelatin zymography analysis of cell culture media and lysates revealed a ~40% increase in gelatinase activity and pharmacological inhibition of MMP2 abolished the Ang II mediated increase in myoblast migration. Ang II also appeared to signal in a paracrine fashion to induce migration as 4h of cyclic mechanical stretch of myoblasts enhanced migration of co‐cultured myoblasts. To test the involvement of Ang II signaling during skeletal muscle regeneration in vivo , control and At1a −/− mice were subjected to cardiotoxin injury. In comparison to controls, at 14 and 21 days following injury, At1a −/− mice demonstrated 34 and 25% reductions in cross sectional area respectively. Taken together, these results demonstrate that Ang II modulates skeletal muscle fibre growth by regulating myoblast chemotaxis through MMP2.