Long noncoding RNA ERLR mediates epithelial-mesenchymal transition of retinal pigment epithelial cells and promotes experimental proliferative vitreoretinopathy.
Long noncoding RNA ERLR mediates epithelial-mesenchymal transition of retinal pigment epithelial cells and promotes experimental proliferative vitreoretinopathy.
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长非编码RNA ERLR介导视网膜色素上皮细胞上皮-间质转化并促进实验性增殖性玻璃体视网膜病变
DOI：
10.1038/s41418-021-00756-5
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发表时间：
2021-08
影响因子：
12.4
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Yang S;Li H;Yao H;Zhang Y;Bao H;Wu L;Zhang C;Li M;Feng L;Zhang J;Zheng Z;Xu G;Wang F
增生性玻璃体视网膜病变（PVR）是一种导致严重失明的疾病，其特征在于形成收缩性纤维化视网膜下膜或视网膜前膜。视网膜色素上皮（RPE）细胞的上皮间质转化（EMT）是PVR的标志。本研究旨在研究一种名为EMT相关lncRNA（ERLR，LINC 01705 -201（ENST00000438158.1））的长链非编码RNA（lncRNA）在PVR中的作用，并探讨其潜在机制。本研究采用lncRNA微阵列和RT-PCR技术检测了转化生长因子β1（transforming growth factor β1，TGF-β1）诱导的RPE细胞ERLR表达上调。进一步的研究表征了全长ERLR，并证实其主要在细胞质中表达。在体外实验中，ERLR的沉默可减弱TGF-β1诱导的EMT，而ERLR的过表达可直接触发RPE细胞的EMT。在体内，抑制RPE细胞中的ERLR降低了细胞诱导实验性PVR的能力。从机制上讲，染色质免疫沉淀（ChIP）分析表明，转录因子TCF 4直接结合到ERLR的启动子区，并促进其转录。ERLR通过直接结合MYH 9蛋白并增加其稳定性来介导EMT。TCF 4和MYH 9也介导TGF-β1诱导的RPE细胞EMT。此外，在与玻璃体PVR样品孵育的RPE细胞中，ERLR也显著增加。在PVR膜的临床样本中，通过荧光原位杂交（FISH）检测ERLR，并与RPE标记物泛细胞角蛋白（pan-CK）共定位。这些结果表明，lncRNAERLR参与TGF-β1诱导的人RPE细胞EMT，并参与PVR。这一发现为PVR的机制和治疗提供了新的见解。
Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.
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影响因子：
3.7
作者：
Li H;Daculsi R;Grellier M;Bareille R;Bourget C;Remy M;Amedee J
通讯作者：
Amedee J
影响因子：
11.4
作者：
St Laurent, Georges;Wahlestedt, Claes;Kapranov, Philipp
通讯作者：
Kapranov, Philipp
影响因子：
3.7
作者：
Dvashi Z;Goldberg M;Adir O;Shapira M;Pollack A
通讯作者：
Pollack A
影响因子：
7.5
作者：
Liu, Longyang;Ning, Yingxia;Zeng, Zhaoyang
通讯作者：
Zeng, Zhaoyang
影响因子：
5.2
作者：
Alves, Cleidson Padua;Fonseca, Aline Simoneti;Silva, Wilson Araujo, Jr.
通讯作者：
Silva, Wilson Araujo, Jr.