Fibroblast Growth Factor 21 Promotes C2C12 Cells Myogenic Differentiation by Enhancing Cell Cycle Exit.

Xinyi Liu,Yongliang Wang,Shuhong Zhao,Xinyun Li

doi:10.1155/2017/1648715

Abstract

Fibroblast growth factor 21 (FGF21), a secretion protein, functions as a pivotal regulator of energy metabolism and is being considered as a therapeutic candidate in metabolic syndromes. However, the roles of FGF21 in myogenic differentiation and cell cycle remain obscure. In this study, we investigated the function of FGF21 in myogenesis and cell cycle exit using C2C12 cell line. Our data showed that the expression of myogenic genes as well as cell cycle exit genes was increased after FGF21 overexpression, and FGF21 overexpression induces cell cycle arrest. Moreover, cell cycle genes were decreased in FGF21 overexpression cells while they were increased in FGF21 knockdown cells. Further, FGF21/P53/p21/Cyclin-CDK has been suggested as the key pathway for cell cycle exit mediated by FGF21 in C2C12 cells. Also, we deduce that FGF21 promotes the initiation of myogenic differentiation mainly through enhancing cell cycle exit of C2C12 cells. Taken together, our results demonstrated that FGF21 promotes cell cycle exit and enhances myogenic differentiation of C2C12 cells. This study provided new evidence that FGF21 promotes myogenic differentiation, which could be useful for better understanding the roles of FGF21 in myogenesis.

Highlights

Fibroblast growth factor 21 (FGF21), a member of the FGF family, was initially identified by Nobuyuki Itoh’s group [1], and its bioactivity was first discovered as a potential regulator of glucose uptake in mouse and human adipocytes [2]
The mRNA levels of cell cycle exit genes P16, P18, P19, and P21 were upregulated during early myogenic differentiation (Figure 1(b))
Western blot results confirmed that FGF21, MEF2c, MyoG, and P21 were upregulated during the early stage of myogenic differentiation, while Cyclin D3 was downregulated (Figure 1(c))

Summary

Introduction

Fibroblast growth factor 21 (FGF21), a member of the FGF family, was initially identified by Nobuyuki Itoh’s group [1], and its bioactivity was first discovered as a potential regulator of glucose uptake in mouse and human adipocytes [2]. Signaling pathway studies indicated that FGF21 could bind fibroblast growth factor receptor (FGFR) 1/2 and coreceptor β-Klotho after being secreted from tissues [3, 4]. FGF21 can be induced in multiple tissues including liver, pancreas, adipose tissue, and skeletal muscle [8,9,10,11,12]. The liver tissue is the major source of FGF21 in the conditions of fasting and ketogenesis [13, 14], while under cold exposure, brown adipose tissue becomes an important organ of FGF21 generation [15]. Circulating FGF21 was increased in several pathological statuses including obesity, diabetes, and other metabolic syndromes in rodents and humans [16,17,18]. The response to exogenous FGF21 is impaired and the expression of FGF21 receptors is reduced [19,20,21]

Methods

Results

Conclusion