Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal
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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.
To delineate the endogenous contribution of preproghrelin in muscle regeneration, we evaluated the repair process in Ghrl−/− mice upon CTX-induced injury.
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.
Although we cannot discern the specific Ghrl-derived peptide responsible for such activities, these data indicate that Ghrl contributes to a proper muscle regeneration.
KeywordsGhrelin knockout Skeletal muscle regeneration Satellite cells Self-renewal
This study was supported by research grants from the Muscular Dystrophy Association (grant MDA294617 to NF and AG), Association Française contre les Myopathies (Grant 16437 to AG), AIRC (to AG), and Fondazione Cariplo (Grant 2015_0634 to NF).
Compliance with ethical standards
Conflict of interest
A.G. is a consultant to Helsinn (Lugano, Switzerland), N.F. is a consultant to Lyric Pharmaceuticals (South San Francisco, CA, USA).
This article does not contain any studies with human participants performed by any of the authors. Animal experiments were performed according to procedures approved by the Institutional Animal Care and Use Committee at the University of Piemonte Orientale.
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