Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways

Shaoting Fu; Xiaojing Lin; Lijun Yin; Xiaohui Wang

doi:10.1186/s12986-021-00610-y

Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways

Nutr Metab (Lond). 2021 Sep 15;18(1):85. doi: 10.1186/s12986-021-00610-y.

Authors

Shaoting Fu^{1

2}, Xiaojing Lin¹, Lijun Yin¹, Xiaohui Wang³

Affiliations

¹ Department of Exercise Physiology, School of Kinesiology, Shanghai University of Sport, 188 Hengren Road, Yangpu District, Shanghai, 200438, China.
² Department of Kinesiology, College of Physical Education, Shanghai Normal University, Shanghai, 200234, China.
³ Department of Exercise Physiology, School of Kinesiology, Shanghai University of Sport, 188 Hengren Road, Yangpu District, Shanghai, 200438, China. wangpan96@126.com.

Abstract

Background: Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR's role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified.

Methods: Firstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch. Then the influences of transfection AR or exogenous IGF-1 treatment on proliferation and these indicators were detected in stretched L6 myoblasts.

Results: (1) Under un-stretched state, the proliferation of L6 was slower than C2C12 cells. Furthermore, AR knockdown in C2C12 myoblasts repressed, while AR overexpression in L6 myoblasts promoted the proliferation. (2) 15% stretch-induced increases in the proliferation and activities of p38 and ERK1/2 were lower in L6 than C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with the increases of p38 and ERK1/2 activities. (3) 20% stretch-induced anti-proliferation and inhibition of p38 activity were severer in L6 than C2C12 myoblasts; AR overexpression reversed the anti-proliferation of 20% stretch and enhanced p38 activity in L6 myoblasts. (4) In stretched L6 myoblasts, AR overexpression increased IGF-1R level despite no detectable IGF-1; and recombinant IGF-1 increased the proliferation, the level of IGF-1R, and the activities of p38 and ERK1/2 in 15% stretched L6 myoblasts.

Conclusions: The study demonstrated AR's crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch's pro-proliferation via activating IGF-1R- p38 and ERK1/2 pathways while decreased AR achieved 20% stretch's anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass.

Keywords: AR; ERK1/2; IGF-1R; Myoblast proliferation; Stretch; p38.

Abstract

Grants and funding