1. Academic Validation
  2. LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway

LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway

  • Exp Cell Res. 2020 Nov 1;396(1):112237. doi: 10.1016/j.yexcr.2020.112237.
Hao-Ke Li 1 Yong Zhou 1 Jian Ding 2 Lei Xiong 1 Ying-Xu Shi 1 Yan-Ji He 1 Dan Yang 1 Zhong-Liang Deng 1 Mao Nie 3 Yan Fei Gao 4
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
  • 2 Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
  • 3 Department of Orthopaedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China. Electronic address: 302218@cqmu.edu.cn.
  • 4 Department of Orthopaedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China. Electronic address: 304034@cqmu.edu.cn.
Abstract

The proliferation and differentiation of myoblast cells are regulated by the Fibroblast Growth Factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

Keywords

FGFR1; LRTM1; Myogenesis; Skeletal muscle.

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