Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells.

Shuai Yang,Hui Li,Haipei Yao,Min Li,Fang Wang,Tiansen Li

doi:10.1371/journal.pone.0152687

Shuai Yang, Hui Li + Show 4 more

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https://doi.org/10.1371/journal.pone.0152687

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Journal: PloS one	Publication Date: Mar 28, 2016
Citations: 58	License type: CC BY 4.0

Affiliation: Shanghai Tenth People's Hospital, Tongji University

Abstract

PurposeTo study the role of long non-coding RNA (lncRNA) MALAT1 in transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells.MethodsARPE-19 cells were cultured and exposed to TGF-β1. The EMT of APRE-19 cells is confirmed by morphological change, as well as the increased expression of alpha-smooth muscle actin (αSMA) and fibronectin, and the down-regulation of E-cadherin and Zona occludin-1(ZO-1) at both mRNA and protein levels. The expression of lncRNA MALAT1 in RPE cells were detected by quantitative real-time PCR. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). The effect of inhibition of MALAT1 on EMT, migration, proliferation, and TGFβ signalings were observed. MALAT1 expression was also detected in primary RPE cells incubated with proliferative vitreoretinopathy (PVR) vitreous samples.ResultsThe expression of MALAT1 is significantly increased in RPE cells incubated with TGFβ1. MALAT1 silencing attenuates TGFβ1-induced EMT, migration, and proliferation of RPE cells, at least partially through activating Smad2/3 signaling. MALAT1 is also significantly increased in primary RPE cells incubated with PVR vitreous samples.ConclusionLncRNA MALAT1 is involved in TGFβ1-induced EMT of human RPE cells and provides new understandings for the pathogenesis of PVR.

Highlights

Proliferative vitreoretinopathy (PVR), a severe blinding disease characterized by the formation of epiretinal membranes through a defective wound repair process, occurs as a complication of rhegmatogenous retinal detachment [1,2]
Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is significantly increased in primary retinal pigment epithelial (RPE) cells incubated with PVR vitreous samples
long noncoding RNAs (LncRNAs) MALAT1 is involved in TGFβ1-induced epithelial-mesenchymal transition (EMT) of human RPE cells and provides new understandings for the pathogenesis of PVR

Summary

Introduction

Proliferative vitreoretinopathy (PVR), a severe blinding disease characterized by the formation of epiretinal membranes through a defective wound repair process, occurs as a complication of rhegmatogenous retinal detachment [1,2]. In the settings of PVR development, RPE cells which exposed to the vitreous (which is rich of cytokines and growth factors) are detached from Bruch’s membrane and migrate into the vitreous through the retina tear [6] In this process, RPE cells undergo a process known as epithelial-mesenchymal transition (EMT), an orchestrated series of events in which fully differentiated epithelial cells undergo transition and acquire a mesenchymal phenotype. Various growth factors/cytokines, intracellular signaling pathways, transcription factors, and microRNAs are indicated to play significant roles in EMT of RPE cells [7,8,9,10,11,12,16]. It is not clear whether long noncoding RNAs (LncRNAs) contribute to EMT of RPE cells

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