Dicer1 facilitates liver regeneration in a manner dependent on the inhibitory effect of miR-21 on Pten and Rhob expression
Dicer1 facilitates liver regeneration in a manner dependent on the inhibitory effect of miR-21 on Pten and Rhob expression
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Dicer1 以依赖于 miR-21 对 Pten 和 Rhob 表达的抑制作用的方式促进肝再生。
DOI：
10.1016/j.lfs.2019.116656
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发表时间：
2019-09-01
期刊：
影响因子：
6.1
通讯作者：
Yang, Jiayin
中科院分区：
文献类型：
--
作者：
Lv, Tao;Kong, Lingxiang;Yang, Jiayin
目的：他莫昔芬诱导成熟小鼠肝脏特异性Dicer1缺失（iDicer1(-/-)）可能为证明Dicer1和mirna的急性缺失在肝脏再生过程中的真正作用提供线索。主要方法：本研究通过Cre/LoxP系统构建他莫昔芬诱导Dicer1缺失小鼠，然后进行经典的70%部分肝切除术或cc14诱导的肝损伤。为了挽救Dicer1消融对肝脏再生的抑制作用，将miR-21 agomir注射到iDicer1（-/-）小鼠的尾静脉中。主要发现：与Dicer1的胚胎组成性缺失不同，他莫昔芬诱导的Dicer1缺失不会导致严重的肝脏损伤或病变，为研究Dicer1和mirna在肝脏再生中的急性缺失提供了理想的模型。Dicer1缺失通过miR-21对PTEN和Rhob表达的抑制作用导致肝脏再生受损。意义：在我们之前的研究中，我们发现胚胎中Dicer1的缺失会损害肝细胞的存活，导致慢性炎症和祖细胞活化，而Dicer1在肝脏再生中的作用在很大程度上仍然未知。我们通过提高miR-21的表达，明确了Dicer1对肝脏再生的促进作用，miR-21抑制了两种阴性细胞增殖调节因子Pten和Rhob的表达。
Aims: Tamoxifen-induced liver-specific Dicer1 deletion (iDicer1(-/-)) in mature mice may provide clues demonstrating the genuine effects of acute loss of Dicer1 and miRNAs in the liver regeneration process.Main methods: In this study, mice with tamoxifen-induced Dicer1 deletion through the Cre/LoxP system were constructed and then underwent classic 70% partial hepatectomy or CC14-induced liver injury. To rescue the inhibitory effect of Dicer1 ablation on liver regeneration, miR-21 agomir was injected into the tail vein of iDicer1(-/-) mice.Key findings: Unlike constitutive embryonic deletion of Dicer1, tamoxifen-induced Dicer1 deletion did not result in severe liver injury or lesions, providing an ideal model for investigating acute loss of Dicer1 and miRNAs in liver regeneration. Dicer1 deletion led to impaired liver regeneration through the inhibitory effect of miR-21 on PTEN and Rhob expression.Significance: In our previous study, we found that embryonic loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation, while the role of Dicer1 in liver regeneration remains largely unknown. We clearly identified the promotion effect of Dicer1 on liver regeneration by increasing miR-21 expression, which inhibits the expression of two negative cell proliferation regulators, Pten and Rhob.