MicroRNA-26a and -26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway.
MicroRNA-26a and -26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway.
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MicroRNA-26a和-26b通过负向调节Jagged-1/Notch信号通路抑制晶状体纤维化和白内障
DOI：
10.1038/cdd.2016.152
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发表时间：
2017-08
影响因子：
12.4
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Chen X;Xiao W;Chen W;Liu X;Wu M;Bo Q;Luo Y;Ye S;Cao Y;Liu Y
纤维化是一种慢性过程，涉及各种器官中多种疾病的发展和进展，几乎占所有已知死亡的一半。上皮间质转化（EMT）是器官纤维化的重要过程。透镜因其独特的生物学特性而成为研究纤维化过程的理想生物学工具。使用功能获得和功能丧失测定以及不同的透镜纤维化模型，在此我们证明了miR-26家族的成员microRNA（miR）-26 a和miR-26 b在EMT和纤维化中具有关键作用。在体内外均能显著抑制透镜上皮细胞的增殖、迁移、EMT和透镜纤维化。有趣的是，我们发现miR-26 a和-26b的抗EMT作用的机制是通过直接靶向Jagged-1和抑制Jagged-1/Notch信号传导。此外，我们提供了在体外和体内的证据，Jagged-1/Notch信号在TGFβ2刺激的EMT中被激活，并且Notch信号的阻断可以逆转透镜上皮细胞（LEC）的EMT和透镜纤维化。鉴于EMT在大多数纤维化疾病、癌症转移和复发中的普遍参与，miR-26家族和Notch途径可能在治疗纤维化疾病和癌症中具有治疗用途。
Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial–mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFβ2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.
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DOI：
10.1016/j.biocel.2006.11.005
发表时间：
2007-01-01
影响因子：
4
作者：
McAnulty, Robin J.
通讯作者：
McAnulty, Robin J.
影响因子：
5.7
作者：
Ru, Peng;Steele, Robert;Ray, Ratna B.
通讯作者：
Ray, Ratna B.
影响因子：
6
作者：
Saika, S;Kono-Saika, S;Roberts, AB
通讯作者：
Roberts, AB
microRNA-26a 在特发性肺纤维化中的抗纤维化作用和机制。
影响因子：
12.4
作者：
Liang, Haihai;Xu, Chaoqian;Du, Zhimin
通讯作者：
Du, Zhimin
影响因子：
2.5
作者：
Chen, X.;Xiao, W.;Liu, Y.
通讯作者：
Liu, Y.