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. 2017 Sep 1;130(17):2833-2842.
doi: 10.1242/jcs.202226. Epub 2017 Jul 21.

Nestin Contributes to Skeletal Muscle Homeostasis and Regeneration

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Free article

Nestin Contributes to Skeletal Muscle Homeostasis and Regeneration

Julia Lindqvist et al. J Cell Sci. .
Free article

Abstract

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.

Keywords: Cdk5; Differentiation; Intermediate filament; Muscle; Nestin; Regeneration.

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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