TNF-α and IGF1 modify the microRNA signature in skeletal muscle cell differentiation

Cell Communication and Signaling

Research

Anna Polesskaya¹  Sebastian Kaiser²  Sabine Krause³  Stefan Bauersachs⁴  Michael W Pfaffl⁵  Swanhild U Meyer⁵  Christian Thirion⁶ 

[1] CNRS FRE 3377, Univ. Paris-Sud, CEA Saclay, iBiTec-S/ SBIGeM, F-91191, Gif-sur-Yvette, France;Department of Statistics, Ludwig-Maximilians-Universität München, Ludwigstr. 33, 80539, Munich, Germany;Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-Universität München, Marchioninistr. 17, 81377, Munich, Germany;Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, 81377, Munich, Germany;Current address: ETH Zurich, Institute of Agricultural Sciences, Animal Physiology, Universitätstrasse 2 / LFW B 58.1, 8092, Zurich, Switzerland;Physiology Weihenstephan, ZIEL Research Center for Nutrition and Food Sciences, Technische Universität München, Weihenstephaner Berg 3, D-85354, Freising, Germany;SIRION Biotech GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany;

关键词: microRNA;    TNF-α;    IGF1;    Skeletal muscle cell;    Expression profiling;    Myoblast differentiation;    Human;    Murine;    miRNA biogenesis;    MAPK;   

DOI  :  10.1186/s12964-015-0083-0

 received in 2014-05-22, accepted in 2015-01-03,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundElevated levels of the inflammatory cytokine TNF-α are common in chronic diseases or inherited or degenerative muscle disorders and can lead to muscle wasting. By contrast, IGF1 has a growth promoting effect on skeletal muscle. The molecular mechanisms mediating the effect of TNF-α and IGF1 on muscle cell differentiation are not completely understood. Muscle cell proliferation and differentiation are regulated by microRNAs (miRNAs) which play a dominant role in this process. This study aims at elucidating how TNF-α or IGF1 regulate microRNA expression to affect myoblast differentiation and myotube formation.ResultsIn this study, we analyzed the impact of TNF-α or IGF1 treatment on miRNA expression in myogenic cells. Results reveal that i) TNF-α and IGF1 regulate miRNA expression during skeletal muscle cell differentiation in vitro, ii) microRNA targets can mediate the negative effect of TNF-α on fusion capacity of skeletal myoblasts by targeting genes associated with axon guidance, MAPK signalling, focal adhesion, and neurotrophin signalling pathway, iii) inhibition of miR-155 in combination with overexpression of miR-503 partially abrogates the inhibitory effect of TNF-α on myotube formation, and iv) MAPK/ERK inhibition might participate in modulating the effect of TNF-α and IGF1 on miRNA abundance.ConclusionsThe inhibitory effects of TNF-α or the growth promoting effects of IGF1 on skeletal muscle differentiation include the deregulation of known muscle-regulatory miRNAs as well as miRNAs which have not yet been associated with skeletal muscle differentiation or response to TNF-α or IGF1. This study indicates that miRNAs are mediators of the inhibitory effect of TNF-α on myoblast differentiation. We show that intervention at the miRNA level can ameliorate the negative effect of TNF-α by promoting myoblast differentiation. Moreover, we cautiously suggest that TNF-α or IGF1 modulate the miRNA biogenesis of some miRNAs via MAPK/ERK signalling. Finally, this study identifies indicative biomarkers of myoblast differentiation and cytokine influence and points to novel RNA targets.

【 授权许可】

CC BY   
© Meyer et al.; licensee BioMed Central. 2015