, Volume 62, Issue 1, pp 129–135 | Cite as

Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal

  • Elia Angelino
  • Simone Reano
  • Alessandro Bollo
  • Michele Ferrara
  • Marilisa De Feudis
  • Hana Sustova
  • Emanuela Agosti
  • Sara Clerici
  • Flavia Prodam
  • Catherine-Laure Tomasetto
  • Andrea GrazianiEmail author
  • Nicoletta FilighedduEmail author
Original Article



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.


Ghrelin 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).

Ethical approval

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.

Supplementary material

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Supplementary Figure


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Elia Angelino
    • 1
    • 2
  • Simone Reano
    • 1
  • Alessandro Bollo
    • 1
    • 2
  • Michele Ferrara
    • 1
    • 2
  • Marilisa De Feudis
    • 1
  • Hana Sustova
    • 1
  • Emanuela Agosti
    • 1
  • Sara Clerici
    • 1
    • 2
  • Flavia Prodam
    • 3
  • Catherine-Laure Tomasetto
    • 4
  • Andrea Graziani
    • 1
    • 2
    Email author
  • Nicoletta Filigheddu
    • 1
    Email author
  1. 1.Department of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly
  2. 2.Università Vita-Salute San RaffaeleMilanoItaly
  3. 3.Department of Health SciencesUniversity of Piemonte OrientaleNovaraItaly
  4. 4.IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire - Université de StrasbourgIllkirchFrance

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