title: Impaired skeletal muscle regeneration in the absence of fibrosis during hibernation in 13-lined ground squirrels.
abstract: Skeletal muscle atrophy can occur as a consequence of immobilization and/or starvation in the majority of vertebrates studied. In contrast, hibernating mammals are protected against the loss of muscle mass despite long periods of inactivity and lack of food intake. Resident muscle-specific stem cells (satellite cells) are known to be activated by muscle injury and their activation contributes to the regeneration of muscle, but whether satellite cells play a role in hibernation is unknown. In the hibernating 13-lined ground squirrel we show that muscles ablated of satellite cells were still protected against atrophy, demonstrating that satellite cells are not involved in the maintenance of skeletal muscle during hibernation. Additionally, hibernating skeletal muscle showed extremely slow regeneration in response to injury, due to repression of satellite cell activation and myoblast differentiation caused by a fine-tuned interplay of p21, myostatin, MAPK, and Wnt signaling pathways. Interestingly, despite long periods of inflammation and lack of efficient regeneration, injured skeletal muscle from hibernating animals did not develop fibrosis and was capable of complete recovery when animals emerged naturally from hibernation. We propose that hibernating squirrels represent a new model system that permits evaluation of impaired skeletal muscle remodeling in the absence of formation of tissue fibrosis.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Andres-Mateos
authors.forename: Rebeca
authors.initials: R
authors.lastname: Mejias
authors.forename: Arshia
authors.initials: A
authors.lastname: Soleimani
authors.forename: Brian M
authors.initials: BM
authors.lastname: Lin
authors.forename: Tyesha N
authors.initials: TN
authors.lastname: Burks
authors.forename: Ruth
authors.initials: R
authors.lastname: Marx
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lin
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zellars
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.forename: Tom G
authors.initials: TG
authors.lastname: Marr
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
authors.forename: Dana K
authors.initials: DK
authors.lastname: Merriman
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Cohn
mesh_terms: D000818:Animals; D005355:Fibrosis; D006605:Hibernation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology; D055435:Myostatin / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D012589:Sciuridae / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D055435:Myostatin