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Ciliary neurotrophic factor (CNTF) promotes skeletal muscle progenitor cell (MPC) viability via the phosphatidylinositol 3‐kinase–Akt pathway
Author(s) -
Hiatt Kelly,
Lewis Davina,
Shew Mathew,
BijangiVishehsaraei Khadijeh,
Halum Stacey
Publication year - 2014
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.1598
Subject(s) - ciliary neurotrophic factor , viability assay , neurotrophic factors , microbiology and biotechnology , protein kinase b , ly294002 , pi3k/akt/mtor pathway , growth factor , signal transduction , biology , chemistry , cell , biochemistry , receptor
Muscle progenitor cells (MPCs) are currently being investigated as cellular vectors to deliver neurotrophic factor (NF) for the promotion of re‐innervation after axonal injury. Ideally NF delivery in such a model would enhance axonal regeneration while simultaneously promoting MPC viability. To date, insulin‐like growth factor 1 (IGF‐1) is one of the few NFs known to promote both re‐innervation and MPC viability. We herein identify ciliary neurotrophic factor (CNTF) as a factor that promotes MPC viability in culture, and demonstrate CNTF to impart greater viability effects on MPCs than IGF‐1. We demonstrate that pharmacological inhibition via LY294002 results in abrogation of CNTF‐mediated viability, suggesting that the CNTF‐mediated MPC viability benefit occurs via the PI3–Akt pathway. Finally, we employ a genetic model, establishing MPC cultures from mice deficient in class I A PI‐3 K ( p85 α −/− ) mice, and demonstrate that the viability benefit imparted by CNTF is completely abrogated in PI‐3 K‐deficient MPCs compared to wild‐type controls. In summary, our investigations define CNTF as a promoter of MPC viability beyond IGF‐1, and reveal that the CNTF‐mediated MPC viability effects occur via the PI3–Akt pathway. Copyright © 2012 John Wiley & Sons, Ltd.