title: Regulation of muscle satellite cell activation and chemotaxis by angiotensin II.
abstract: The role of angiotensin II (Ang II) in skeletal muscle is poorly understood. We report that pharmacological inhibition of Ang II signaling or ablation of the AT1a receptor significantly impaired skeletal muscle growth following myotrauma, in vivo, likely due to impaired satellite cell activation and chemotaxis. In vitro experiments demonstrated that Ang II treatment activated quiescent myoblasts as evidenced by the upregulation of myogenic regulatory factors, increased number of β-gal+, Myf5-LacZ myoblasts and the acquisition of cellular motility. Furthermore, exogenous treatment with Ang II significantly increased the chemotactic capacity of C2C12 and primary cells while AT1a(-/-) myoblasts demonstrated a severe impairment in basal migration and were not responsive to Ang II treatment. Additionally, Ang II interacted with myoblasts in a paracrine-mediated fashion as 4 h of cyclic mechanical stimulation resulted in Ang II-induced migration of cocultured myoblasts. Ang II-induced chemotaxis appeared to be regulated by multiple mechanisms including reorganization of the actin cytoskeleton and augmentation of MMP2 activity. Collectively, these results highlight a novel role for Ang II and ACE inhibitors in the regulation of skeletal muscle growth and satellite cell function.
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, Canada.
authors.forename: Adam P W
authors.initials: AP
authors.lastname: Johnston
authors.forename: Jeff
authors.initials: J
authors.lastname: Baker
authors.forename: Leeann M
authors.initials: LM
authors.lastname: Bellamy
authors.forename: Bryon R
authors.initials: BR
authors.lastname: McKay
authors.forename: Michael
authors.initials: M
authors.lastname: De Lisio
authors.forename: Gianni
authors.initials: G
authors.lastname: Parise
mesh_terms: D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D002633:Chemotaxis; D018920:Coculture Techniques; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000166:cytology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*
chemical_list: D000199:Actins; D017931:DNA Primers; D000804:Angiotensin II