MicroRNA 322 Aggravates Dexamethasone-Induced Muscle Atrophy by Targeting IGF1R and INSR
MicroRNA 322 Aggravates Dexamethasone-Induced Muscle Atrophy by Targeting IGF1R and INSR
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MicroRNA 322 通过靶向 IGF1R 和 INSR 加剧地塞米松引起的肌肉萎缩
DOI：
10.3390/ijms21031111
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发表时间：
2020-02-01
影响因子：
5.6
通讯作者：
Hao, Linlin
中科院分区：
文献类型：
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作者：
Geng, Hongwei;Song, Qinglong;Hao, Linlin
地塞米松（Dex）作为一种有效的抗炎、抗休克和免疫抑制剂已被广泛使用。然而，大剂量或长期使用右美托咪定伴有包括骨骼肌萎缩在内的副作用，其潜在机制尚不完全清楚。许多microRNAs （miRNAs）已被证明在骨骼肌萎缩中发挥关键作用。先前的研究表明，在dex处理的C2C12肌管中，miR-322的表达显著增加。在我们的研究中，Dex需要糖皮质激素受体（GR）才能增加miR-322在C2C12肌管中的表达。miR-322 mimic或miR-322 inhibitor被用于调节miR-322的表达。通过荧光素酶报告基因检测，发现胰岛素样生长因子1受体（IGF1R）和胰岛素受体（INSR）是miR-322的靶基因，并在dexx诱导的肌肉萎缩中发挥关键作用。miR-322过表达促进dex处理小鼠C2C12肌管和腓肠肌萎缩。相反，miR-322抑制表现出相反的效果。这些数据表明，miR-322通过靶向IGF1R和INSR参与dex诱导的肌肉萎缩。此外，miR-322可能是对抗dex诱导的肌肉萎缩的潜在靶点。抑制miR-322也可能是dex诱导的肌肉萎缩的一种治疗方法。
Dexamethasone (Dex) has been widely used as a potent anti-inflammatory, antishock, and immunosuppressive agent. However, high dose or long-term use of Dex is accompanied by side effects including skeletal muscle atrophy, whose underlying mechanisms remain incompletely understood. A number of microRNAs (miRNAs) have been shown to play key roles in skeletal muscle atrophy. Previous studies showed significantly increased miR-322 expression in Dex-treated C2C12 myotubes. In our study, the glucocorticoid receptor (GR) was required for Dex to increase miR-322 expression in C2C12 myotubes. miR-322 mimic or miR-322 inhibitor was used for regulating the expression of miR-322. Insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (INSR) were identified as target genes of miR-322 using luciferase reporter assays and played key roles in Dex-induced muscle atrophy. miR-322 overexpression promoted atrophy in Dex-treated C2C12 myotubes and the gastrocnemius muscles of mice. Conversely, miR-322 inhibition showed the opposite effects. These data suggested that miR-322 contributes to Dex-induced muscle atrophy via targeting of IGF1R and INSR. Furthermore, miR-322 might be a potential target to counter Dex-induced muscle atrophy. miR-322 inhibition might also represent a therapeutic approach for Dex-induced muscle atrophy.