ISLR regulates skeletal muscle atrophy via IGF1-PI3K/Akt-Foxo signaling pathway
ISLR regulates skeletal muscle atrophy via IGF1-PI3K/Akt-Foxo signaling pathway
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DOI：
10.1007/s00441-020-03251-4
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发表时间：
2020-07-21
影响因子：
3.6
通讯作者：
Yin, Huadong
中科院分区：
文献类型：
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作者：
Cui, Can;Han, Shunshun;Yin, Huadong
含有富含亮氨酸重复序列的免疫球蛋白超家族（Islr）包含Ig样结构域、LRR基序和跨膜结构域，并且在多种鸡组织中高度表达。尽管Islr在肌肉再生中具有已知的作用，但其在肌肉萎缩的调节中的作用尚未被研究。在这项研究中，我们构建了Islr沉默或Islr过表达的成肌细胞，以研究其在成肌细胞分化成肌管过程中的作用。结果表明，Islr在鸡骨骼肌组织中高表达，对成肌细胞的分化有调节作用，但对成肌细胞的增殖无影响。Islr可调节肌萎缩相关基因atrogin-1和MuRF-1的表达，并可挽救地塞米松诱导的成肌细胞和肌管萎缩。Western blot分析表明Islr通过IGF/PI 3 K/AKT-FOXO信号通路参与成肌细胞萎缩。同时，caspase-8和caspase-9的表达在Islr沉默组中增加，表明其在细胞活力中的作用。综上所述，Islr在成肌细胞分化过程中发挥重要作用，并通过IGF/PI 3 K/AKT-FOXO信号通路减轻骨骼肌萎缩，防止肌细胞凋亡。
Immunoglobulin superfamily containing leucine-rich repeat (Islr) contains an Ig-like domain, an LRR motif, and a transmembrane domain and is highly expressed in various chicken tissues. Although Islr has known roles in muscle regeneration, its role in the regulation of muscle atrophy has not been studied. In this study, we constructed Islr-silenced or Islr-overexpressed myoblasts to investigate its role during the differentiation of myoblasts into myotubes. The results showed that Islr was highly expressed in chicken skeletal muscle tissue and regulated myoblast differentiation, but not proliferation. Islr regulated the expression of atrophy-related genes including atrogin-1 and MuRF-1, and could rescue dexamethasone-induced atrophy in myoblasts and myotubes. Western blot analysis indicated that Islr participates in myoblast atrophy through IGF/PI3K/AKT-FOXO signaling. Meanwhile, the expression of caspase-8 and caspase-9 increased in Islr-silenced groups, indicating its role in cell viability. Taken together, these data suggested that Islr plays an important role in myoblasts differentiation, and which can alleviate skeletal muscle atrophy and prevents muscle cell apoptosis via IGF/PI3K/AKT-FOXO signaling pathway.