4.5 Article

Progranulin compensates for blocked IGF-1 signaling to promote myotube hypertrophy in C2C12 myoblasts via the PI3K/Akt/mTOR pathway

Journal

FEBS LETTERS
Volume 586, Issue 19, Pages 3485-3492

Publisher

WILEY
DOI: 10.1016/j.febslet.2012.07.077

Keywords

Progranulin; IGF-1; Muscle hypertrophy; C2C12 myoblast; Signaling

Funding

  1. National Science Council [NSC98-2321-B-001-026-MY3, NSC 100-2324-B-020-001-CC1]

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It is well known that growth hormone (GH)-induced IGF-1 signaling plays a dominant role in postnatal muscle growth. Our previous studies have identified a growth factor, progranulin (PGRN), that is co-induced with IGF-1 upon GH administration. This result prompted us to explore the function of PGRN and its association with IGF-1. In the present study, we demonstrated that, similar to IGF-1, PGRN can promote C2C12 myotube hypertrophy via the PI(3)K/Akt/mTOR pathway. Moreover, PGRN can rescue the muscle atrophy phenotypes in C2C12 myotube when IGF-1 signaling is blocked. This result shows that PGRN can substitute for IGF-1 signaling in the regulation of muscle growth. Our findings provide new insights into IGF-1-modulated complicated networks that regulate muscle growth. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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