miR-24 and miR-122 Negatively Regulate the Transforming Growth Factor-β/Smad Signaling Pathway in Skeletal Muscle Fibrosis.
miR-24 and miR-122 Negatively Regulate the Transforming Growth Factor-β/Smad Signaling Pathway in Skeletal Muscle Fibrosis.
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miR-24 和 miR-122 负向调节骨骼肌纤维化中的转化生长因子-β/Smad 信号通路
DOI：
10.1016/j.omtn.2018.04.005
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发表时间：
2018-06-01
期刊：
影响因子：
--
通讯作者：
Ying H
中科院分区：
文献类型：
--
作者：
Sun Y;Wang H;Li Y;Liu S;Chen J;Ying H
纤维化在骨骼肌损伤后很常见，破坏组织再生和功能。骨骼肌纤维化的潜在机制仍不清楚。转化生长因子-β/Smad信号通路被认为在其中起着关键作用。然而，microRNA如何与转化生长因子-β/Smad相关的肌肉纤维化相互作用仍不清楚。我们发现microRNA（miR）-24-3p和miR-122- 5 p在骨骼肌纤维化中下降，这是转化生长因子-β的结果。上调Smad 4抑制了两种microRNA，而抑制Smad 4则升高了microRNA。荧光素酶报告基因分析和染色质免疫沉淀证实Smad 4直接抑制两种microRNA。另一方面，这两种miR的过表达延缓了纤维化过程。我们进一步确定Smad 2是miR-24- 3 p的直接靶点，而miR-122- 5 p靶向转化生长因子-β受体-II。这两个靶点都是转化生长因子-β/Smad信号转导的重要参与者。综上所述，确定了骨骼肌纤维化中转化生长因子-β/Smad 4信号通路的正反馈环。microRNA可下调TGF-β/Smad轴表达。然而，这种作用被转化生长因子-β下游的Smad 4抑制。
Fibrosis is common after skeletal muscle injury, undermining tissue regeneration and function. The mechanism underlying skeletal muscle fibrosis remains unveiled. Transforming growth factor-β/Smad signaling pathway is supposed to play a pivotal role. However, how microRNAs interact with transforming growth factor-β/Smad-related muscle fibrosis remains unclear. We showed that microRNA (miR)-24-3p and miR-122-5p declined in skeletal muscle fibrosis, which was a consequence of transforming growth factor-β. Upregulating Smad4 suppressed two microRNAs, whereas inhibiting Smad4 elevated microRNAs. Luciferase reporter assay and chromatin immunoprecipitation confirmed that Smad4 directly inhibited two microRNAs. On the other hand, overexpression of these two miRs retarded fibrotic process. We further identified that Smad2 was a direct target of miR-24-3p, whereas miR-122-5p targeted transforming growth factor-β receptor-II. Both targets were important participants in transforming growth factor-β/Smad signaling. Taken together, a positive feedback loop in transforming growth factor-β/Smad4 signaling pathway in skeletal muscle fibrosis was identified. Transforming growth factor-β/Smad axis could be downregulated by microRNAs. This effect, however, was suppressed by Smad4, the downstream of transforming growth factor-β.
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DOI：
10.12659/msm.897909
发表时间：
2016-04-07
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Huang QK;Qiao HY;Fu MH;Li G;Li WB;Chen Z;Wei J;Liang BS
通讯作者：
Liang BS
SB431542抑制小鼠胚胎干细胞分化的机制
影响因子：
4.8
作者：
Du, Juan;Wu, Yongyan;Guo, Zekun
通讯作者：
Guo, Zekun
MicroRNA-24通过靶向p53增加肝细胞癌细胞转移和侵袭：miR-24靶向p53
影响因子：
7.5
作者：
Chen, Li;Luo, Liang;Huang, Xiao-Hui
通讯作者：
Huang, Xiao-Hui
影响因子：
2.9
作者：
Chan, Yi-Sheng;Hsu, Kuo-Yao;Ueng, Steve Wen-Neng
通讯作者：
Ueng, Steve Wen-Neng
影响因子：
3.3
作者：
Kasemkijwattana, C;Menetrey, J;Huard, J
通讯作者：
Huard, J