MicroRNA-24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN.
MicroRNA-24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN.
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DOI：
10.1002/jcp.22476
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发表时间：
2011-05
影响因子：
5.6
通讯作者：
Gonzalez, Pedro
中科院分区：
文献类型：
--
作者：
Luna, Coralia;Li, Guorong;Qiu, Jianming;Epstein, David L.;Gonzalez, Pedro
循环机械应力（CMS）导致sq1改变小梁网（TM）的细胞功能，包括tgf - β1的上调，这可能有助于青光眼的发病机制。尽管已知microRNAs （miRNAs）在许多生物学功能中发挥重要作用，但对其在机械应力引起的细胞反应中的潜在参与知之甚少。我们分析了CMS诱导的miRNA表达变化，并探讨了miR-24在人TM细胞对CMS的反应中可能发挥的作用。CMS诱导miR-24的表达，导致枯草杆菌样蛋白转化酶FURIN的下调，而FURIN在tgf - β1的加工过程中起主要作用。通过3 ' UTR荧光素酶测定和western blot证实FURIN是miR-24的新靶点。过表达miR-24导致活化的tgf - β1显著降低。siRNA对FURIN的下调可以模拟这种效应。相反，用特定的安塔戈莫抑制miR-24的表达会导致tgf - β1的少量但显著增加。此外，miR-24可以阻止CMS诱导的HTM细胞中活性tgf - β1的增加。总之，我们的研究结果表明，mirna可能有助于调节TM细胞对CMS的反应。具体来说，miR-24可能通过直接靶向FURIN，在CMS介导的tgf - β1诱导中发挥重要作用。
Cyclic mechanical stress (CMS) leadsQ1 to alterations of cellular functions in the trabecular meshwork (TM), including the up-regulation of transforming growth factor beta 1 (TGFβ1), that can potentially contribute to the pathogenesis of glaucoma. Although microRNAs (miRNAs) are known to play important roles in many biological functions, little is known about their potential involvement in the cellular responses elicited by mechanical stress. Here we analyzed changes in miRNA expression induced by CMS, and examined the possible role of miR-24 in the response of human TM cells to CMS. CMS induced the expression of miR-24 that led to the down regulation of the subtilisin-like proprotein convertase FURIN, which is known to play a major role in the processing of TGFβ1. FURIN was confirmed as a novel target of miR-24 by 3′ UTR luciferase assay and western blot. Overexpression of miR-24 resulted in a significant decrease in activated TGFβ1. This effect was mimicked by down regulation of FURIN by siRNA. Conversely, inhibition of miR-24 expression with a specific antagomir led to a small but significant increase in TGFβ1. Furthermore, the increase in active TGFβ1 induced by CMS in HTM cells was prevented by miR-24. Altogether, our results suggest that miRNAs might contribute to the regulation of responses to CMS in TM cells. Specifically, miR-24 might play an important role in modulating the induction of TGFβ1 mediated by CMS through direct targeting of FURIN.
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影响因子：
3.3
作者：
Fatma N;Kubo E;Toris CB;Stamer WD;Camras CB;Singh DP
通讯作者：
Singh DP
影响因子：
6.4
作者：
Huang, Shenglin;He, Xianghuo;Gu, Jianren
通讯作者：
Gu, Jianren
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO
影响因子：
5
作者：
Cheng, Yunhui;Liu, Xiaojun;Zhang, Shuo;Lin, Ying;Yang, Jian;Zhang, Chunxiang
通讯作者：
Zhang, Chunxiang
影响因子：
4.8
作者：
Kassiri, Zamaneh;Defamie, Virginie;Khokha, Rama
通讯作者：
Khokha, Rama