FGF13 regulates proliferation and differentiation of skeletal muscle by down‐regulating Spry1. (31st July 2015)

• Record Type: Journal Article
• Authors: Lu, Hongzhao; Shi, Xine; Wu, Guofang; Zhu, Jiayu; Song, Chengchuang; Zhang, Qiangling; Yang, Gongshe
• Is Part Of: Cell proliferation. Volume 48:Number 5(2015:Oct.)
• Page Start: 550
• Page End: 560
• Publication Date: 2015-07-31
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12200
• Languages: English
• ISSNs: 0960-7722

Abstract

<abstract abstract-type="main" id="cpr12200-abs-0001"> <title>Abstract</title> <sec id="cpr12200-sec-0001" sec-type="section"> <title>Objectives</title> <p>Generally, the secretory forms of FGF are known to regulate cell proliferation, differentiation and morphogenesis by binding to the extracellular domain of cell surface receptors. Intracellular FGFs (FGF11‐14) are expressed principally in the nervous system. FGF13 is a microtubule‐stabilizing protein that regulates neuronal polarization and migration. Previous studies have reported high expression of FGF13 in cultures of single muscle fibres. However, functions of FGF13 in muscle development have not been explored.</p> </sec> <sec id="cpr12200-sec-0002" sec-type="section"> <title>Materials and methods</title> <p>Real‐time RT‐PCR was performed to detect expression of <italic>FGF13</italic> during C2C12 muscle cell proliferation and differentiation. To further understand the role of FGF13, its effects on proliferation and differentiation were examined by western blot analyses of cells transfected with <italic>FGF13</italic> siRNA or <italic>FGF13</italic> expression plasmids, or treated with chemical MEK inhibitors. Effects of FGF13 on related signalling pathways in C2C12 cell proliferation and differentiation were determined.</p> </sec> <sec id="cpr12200-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>FGF13</italic> inhibited C2C12 cell proliferation by up‐regulating <italic>p27 </italic>mRNA level and by down‐regulating Cyclin E protein expression, during cell proliferation. Additionally, <italic>FGF13</italic> down‐regulated <italic>Spry1</italic> protein expression, activating the ERK1/2 pathway by phosphorylation and leading to C2C12 cell differentiation inhibition. Consequently, <italic>FGF13</italic> seemed to function as a repressor of myoblast differentiation <italic>via</italic> the ERK1/2 pathway. Although <italic>FGF13</italic> inhibited <italic>Spry1</italic> regardless of cell proliferation or differentiation, its pathway activation occurred only during the stage of myoblast differentiation.</p> </sec> <sec id="cpr12200-sec-0004" sec-type="section"> <title>Conclusions</title> <p> <italic>FGF13</italic> inhibited C2C12 cell proliferation and differentiation by down‐regulating <italic>Spry1</italic>. These findings indicate that <italic>FGF13</italic> played a negative regulatory role in skeletal muscle development.</p> </sec> </abstract>