Ghrelin knockout mice display defective skeletal muscle
regeneration and impaired satellite cell self-renewal
Marilisa De Feudis
Received: 19 January 2018 / Accepted: 15 April 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
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
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.
Keywords Ghrelin knockout
Skeletal muscle regeneration
Skeletal muscle is a plastic tissue that regenerates upon
injury through the activation, expansion, and differentiation
of satellite cells (SCs), myogenic precursors characterized
by the expression of the transcriptional factor Pax7 .
Muscle damage induces a local release of several factors
that activate SCs, eventually leading to repair of the injured
muscle. Ghrl and preproghrelin are induced by injury [2, 3],
and both unacylated ghrelin (UnAG) and obestatin (Ob),
two products of the ghrelin gene, are among the factors
participating in muscle regeneration, as they increase SC
These authors contributed equally: Elia Angelino, Simone Reano.
These authors jointly supervised this work: Andrea Graziani, Nicoletta
Elia Angelino, Simone Reano, Michele Ferrara, Marilisa De Feudis,
Hana Sustova, Emanuela Agosti, Andrea Graziani, and Nicoletta
Filigheddu are members of Istituto Interuniversitario di Miologia
* Andrea Graziani
* Nicoletta Filigheddu
Department of Translational Medicine, University of Piemonte
Orientale, Novara, Italy
Università Vita-Salute San Raffaele, Milano, Italy
Department of Health Sciences, University of Piemonte Orientale,
IGBMC - Institut de Génétique et de Biologie Moléculaire et
Cellulaire - Université de Strasbourg, Illkirch, France
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s12020-018-1606-4) contains supplementary
material, which is available to authorized users.