Caspase-3, myogenic transcription factors and cell cycle inhibitors are regulated by leukemia inhibitory factor to mediate inhibition of myogenic differentiation.

Liam C. Hunt, Aradhana Upadhyay, Jalal Jazayeri, Elizabeth M. Tudor, Jason, D. White

Research output: Contribution to journalArticle

24 Citations (Scopus)
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Abstract

Leukemia inhibitory factor (LIF) is known to inhibit myogenic differentiation as well as to inhibit apoptosis and caspase-3 activation in non-differentiating myoblasts. In addition caspase-3 activity is required for myogenic differentiation. Therefore the aim of this study was to further investigate mechanisms of the differentiation suppressing effect of LIF in particular the possibility of a caspase-3 mediated inhibition of differentiation. Results LIF dependent inhibition of differentiation appeared to involve several mechanisms. Differentiating myoblasts that were exposed to LIF displayed increased transcripts for c-fos. Transcripts for the cell cycle inhibitor p21 as well as muscle regulatory factors myoD and myogenin were decreased with LIF exposure. However, LIF did not directly induce a proliferative effect under differentiation conditions, but did prevent the proportion of myoblasts that were proliferating from decreasing as differentiation proceeded. LIF stimulation decreased the percentage of cells positive for active caspase-3 occurring during differentiation. Both the effect of LIF inhibiting caspase-3 activation and differentiation appeared dependent on mitogen activated protein kinase and extracellular signal regulated kinase kinase (MEK) signalling. The role of LIF in myogenic differentiation was further refined to demonstrate that myoblasts are unlikely to secrete LIF endogenously. Conclusions Altogether this study provides a more comprehensive view of the role of LIF in myogenic differentiation including LIF andthe link between caspase-3 activation, apoptosis and myogenic differentiation.
Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalSkeletal Muscle
Volume1
Issue number1
DOIs
Publication statusPublished - Apr 2011

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