A1 Refereed original research article in a scientific journal
Nestin contributes to skeletal muscle homeostasis and regeneration
Authors: Lindqvist J, Torvaldson E, Gullmets J, Karvonen H, Nagy A, Taimen P, Eriksson JE
Publisher: COMPANY OF BIOLOGISTS LTD
Publication year: 2017
Journal: Journal of Cell Science
Journal name in source: JOURNAL OF CELL SCIENCE
Journal acronym: J CELL SCI
Volume: 130
Issue: 17
First page : 2833
Last page: 2842
Number of pages: 10
ISSN: 0021-9533
DOI: https://doi.org/10.1242/jcs.202226
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/26621223
Nestin, a member of the cytoskeletal family of intermediate filaments, regulates the onset of myogenic differentiation through bidirectional signaling with the kinase Cdk5. Here, we show that these effects are also reflected at the organism level, as there is a loss of skeletal muscle mass in nestin(-/-) (NesKO) mice, reflected as reduced lean (muscle) mass in the mice. Further examination of muscles in male mice revealed that these effects stemmed from nestin- deficient muscles being more prone to spontaneous regeneration. When the regeneration capacity of the compromised NesKO muscle was tested by muscle injury experiments, a significant healing delay was observed. NesKO satellite cells showed delayed proliferation kinetics in conjunction with an elevation in p35 (encoded by Cdk5r1) levels and Cdk5 activity. These results reveal that nestin deficiency generates a spontaneous regenerative phenotype in skeletal muscle that relates to a disturbed proliferation cycle that is associated with uncontrolled Cdk5 activity.
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