Elia Angelino1,2, Simone Reano1, Alessandro Bollo1,2, Michele Ferrara1,2, Marilisa De Feudis1, Hana Sustova1, Emanuela Agosti1, Sara Clerici1,2, Flavia Prodam3, Catherine-Laure Tomasetto4, Andrea Graziani5,6, Nicoletta Filigheddu7. 1. Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. 2. Università Vita-Salute San Raffaele, Milano, Italy. 3. Department of Health Sciences, University of Piemonte Orientale, Novara, Italy. 4. IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire - Université de Strasbourg, Illkirch, France. 5. Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. graziani.andrea@hsr.it. 6. Università Vita-Salute San Raffaele, Milano, Italy. graziani.andrea@hsr.it. 7. Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. nicoletta.filigheddu@med.uniupo.it.
Abstract
PURPOSE: Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. The peptides produced by the ghrelin gene, i.e., acylated ghrelin (AG), unacylated ghrelin (UnAG), and obestatin (Ob), affect skeletal muscle biology in several ways, not always with overlapping effects. In particular, UnAG and Ob promote SC self-renewal and myoblast differentiation, thus fostering muscle regeneration. METHODS: To delineate the endogenous contribution of preproghrelin in muscle regeneration, we evaluated the repair process in Ghrl-/- mice upon CTX-induced injury. RESULTS: Although muscles from Ghrl-/- mice do not visibly differ from WT muscles in term of weight, structure, and SCs content, muscle regeneration after CTX-induced injury is impaired in Ghrl-/- mice, indicating that ghrelin-derived peptides actively participate in muscle repair. Remarkably, the lack of ghrelin gene impacts SC self-renewal during regeneration. CONCLUSIONS: Although we cannot discern the specific Ghrl-derived peptide responsible for such activities, these data indicate that Ghrl contributes to a proper muscle regeneration.
PURPOSE: Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. The peptides produced by the ghrelin gene, i.e., acylated ghrelin (AG), unacylated ghrelin (UnAG), and obestatin (Ob), affect skeletal muscle biology in several ways, not always with overlapping effects. In particular, UnAG and Ob promote SC self-renewal and myoblast differentiation, thus fostering muscle regeneration. METHODS: To delineate the endogenous contribution of preproghrelin in muscle regeneration, we evaluated the repair process in Ghrl-/- mice upon CTX-induced injury. RESULTS: Although muscles from Ghrl-/- mice do not visibly differ from WT muscles in term of weight, structure, and SCs content, muscle regeneration after CTX-induced injury is impaired in Ghrl-/- mice, indicating that ghrelin-derived peptides actively participate in muscle repair. Remarkably, the lack of ghrelin gene impacts SC self-renewal during regeneration. CONCLUSIONS: Although we cannot discern the specific Ghrl-derived peptide responsible for such activities, these data indicate that Ghrl contributes to a proper muscle regeneration.
Authors: Uxía Gurriarán-Rodríguez; Icía Santos-Zas; Omar Al-Massadi; Carlos S Mosteiro; Daniel Beiroa; Rubén Nogueiras; Ana B Crujeiras; Luisa M Seoane; José Señarís; Tomás García-Caballero; Rosalía Gallego; Felipe F Casanueva; Yolanda Pazos; Jesús P Camiña Journal: J Biol Chem Date: 2012-09-19 Impact factor: 5.157