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Nestin contributes to skeletal muscle homeostasis and regeneration




TekijätLindqvist J, Torvaldson E, Gullmets J, Karvonen H, Nagy A, Taimen P, Eriksson JE

KustantajaCOMPANY OF BIOLOGISTS LTD

Julkaisuvuosi2017

JournalJournal of Cell Science

Tietokannassa oleva lehden nimiJOURNAL OF CELL SCIENCE

Lehden akronyymiJ CELL SCI

Vuosikerta130

Numero17

Aloitussivu2833

Lopetussivu2842

Sivujen määrä10

ISSN0021-9533

DOIhttps://doi.org/10.1242/jcs.202226

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/26621223


Tiivistelmä
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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