The microRNAs miR-302d and miR-93 inhibit TGFB-mediated EMT and VEGFA secretion from ARPE-19 cells.


Journal

Experimental eye research
ISSN: 1096-0007
Titre abrégé: Exp Eye Res
Pays: England
ID NLM: 0370707

Informations de publication

Date de publication:
12 2020
Historique:
received: 07 02 2020
revised: 31 07 2020
accepted: 18 09 2020
pubmed: 28 9 2020
medline: 2 3 2021
entrez: 27 9 2020
Statut: ppublish

Résumé

The transforming growth factor-beta (TGFB) plays an essential role in the pathogenesis of some ophthalmologic diseases, including neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR). TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor, which together activate several genes, including VEGFA. TGFB treated ARPE-19 cells show an increased proliferation rate and undergo epithelial to mesenchymal transition (EMT). Since microRNAs (miRNAs) are capable of inhibiting the translation of multiple genes, we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels. In this study, we focused on two miRNAs, miR-302d and miR-93, which inhibit TGFB signalling pathway and therefore TGFB-induced EMT transition as well as VEGFA secretion from ARPE-19 cells. Furthermore, we could show that both miRNAs can retransform TGFB-stimulated mesenchymal ARPE-19 cells towards the morphological epithelial-like state. Taken together, transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies.

Identifiants

pubmed: 32980316
pii: S0014-4835(20)30516-9
doi: 10.1016/j.exer.2020.108258
pii:
doi:

Substances chimiques

MIRN93 microRNA, human 0
MicroRNAs 0
Transforming Growth Factor beta 0
Vascular Endothelial Growth Factor A 0
RNA 63231-63-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

108258

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Heiko R Fuchs (HR)

Institute of Experimental Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, 30625, Germany. Electronic address: fuchs.heiko@mh-hannover.de.

Roland Meister (R)

Institute of Experimental Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, 30625, Germany.

Rishikesh Lotke (R)

Institute of Experimental Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, 30625, Germany.

Carsten Framme (C)

Institute of Experimental Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, 30625, Germany.

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Classifications MeSH