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
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LRTM1通过负向调节FGFR1信号通路促进成肌细胞分化
DOI：
10.1016/j.yexcr.2020.112237
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发表时间：
2020
影响因子：
3.7
通讯作者：
Yan-Fei Gao
中科院分区：
文献类型：
--
作者：
Hao-Ke Li;Yong Zhou;Jian Ding;Lei Xiong;Ying-Xu Shi;Yan-Ji He;Dan Yang;Zhong-Liang Deng;Mao Nie;Yan-Fei Gao
成肌细胞的增殖和分化受成纤维细胞生长因子受体（FGFR）信号通路的调控。尽管FGFR信号级联的调控已被广泛研究，但其在骨骼肌肌生成中的抑制机制仍不清楚。在这项研究中，我们确定了LRTM1， FGFR信号通路的抑制调节剂，负向调节ERK的激活，促进成肌细胞的分化。LRTM1在损伤后成肌细胞分化和骨骼肌再生过程中动态表达。在小鼠成肌细胞C2C12中，敲除（KO） flrtm1可显著抑制成肌细胞的分化；这种效应与MyoD转录活性的降低和ERK激酶的过度激活有关。值得注意的是，进一步的研究表明LRTM1与p52Shc结合，抑制p52Shc向FGFR1募集。综上所述，我们的研究结果确定了FGFR1的一种新的负调节因子，它在调节成肌细胞的分化中起重要作用。
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) ofLrtm1significantly 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.