Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro-The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo.

Natalia Leciejewska,Tomasz P Lehmann,Paweł A Kołodziejski,Bartosz Gawęda,Maciej Głowacki,Ewa Pruszyńska-Oszmałek,Maciej Sassek,Karolina Mielnik,Krzysztof W Nowak,Dawid Szczepankiewicz

doi:10.3390/genes13010081

Abstract

SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells (p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD (p < 0.01). SPX consequently promoted myoblast fusion into the myotubule (p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle.

Highlights

IntroductionIn 2007, using bioinformatics techniques, a novel, highly conservative 14-amino-acid peptide was discovered [1]
We found that GalR2 and GalR3 mRNAs and proteins were expressed in C2C12 cells
These results confirmed previous discoveries which showed that GalR2 and GalR3 are present in C2C12 cells

Summary

Introduction

In 2007, using bioinformatics techniques, a novel, highly conservative 14-amino-acid peptide was discovered [1]. This peptide was called spexin (SPX) or neuropeptide q (NPQ). The tissue expression of this peptide is very widespread in both human and animal organisms. Its presence has been demonstrated in tissues involved in the regulation of carbohydrate–lipid metabolism, such as the liver, adipose tissue, pancreas, kidneys, muscle tissue and tissues of the gastrointestinal tract of the stomach in addition to the small and large intestines [2,3]

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