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Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways

PURPOSE: Our previous study showed that apelin was increased in the vitreous and fibrotic membranes of patients with proliferative diabetic retinopathy (PDR) in vivo, which suggested that apelin may be involved in the development of PDR. In this study, we investigated whether the expression of apeli...

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Autores principales: Qin, Dong, Zheng, Xiao-xue, Jiang, Yan-rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820432/
https://www.ncbi.nlm.nih.gov/pubmed/24227918
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author Qin, Dong
Zheng, Xiao-xue
Jiang, Yan-rong
author_facet Qin, Dong
Zheng, Xiao-xue
Jiang, Yan-rong
author_sort Qin, Dong
collection PubMed
description PURPOSE: Our previous study showed that apelin was increased in the vitreous and fibrotic membranes of patients with proliferative diabetic retinopathy (PDR) in vivo, which suggested that apelin may be involved in the development of PDR. In this study, we investigated whether the expression of apelin was upregulated in human retinal pigment epithelial (RPE) cells in vitro under high glucose conditions. Furthermore, to explore the role of apelin in RPE cells, we investigated the effect of exogenous recombinant apelin on proliferation, migration, and collagen I (a major component of extracellular matrix molecules, associated with PDR) expression and investigated the signaling pathways involved in these processes. METHODS: Real-time PCR and western blot were performed to determine the apelin expression in ARPE-19 cells under high glucose conditions. Exogenous recombinant apelin was used to study the effect of apelin on ARPE-19 cells in vitro. Cell proliferation, migration, and collagen I expression were assessed using an MTT assay, a transwell assay, and real-time PCR analysis. LY294002 (an inhibitor of phosphatidylinositol 3-kinase) and PD98059 (an inhibitor of mitogen-activated protein kinase) were used to help to determine the apelin signaling mechanism. RESULTS: High glucose upregulated apelin expression in RPE cells. Exogenous recombinant apelin activated protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation and promoted proliferation, migration, and collagen I expression in RPE cells. Pretreatment with LY294002 and PD98059 abolished apelin-induced activation of Akt and Erk, proliferation, and collagen I expression. Apelin-induced migration was partially blocked by pretreatment with LY294002 and PD98059. CONCLUSIONS: The expression of apelin was upregulated under high glucose conditions in RPE cells in vitro. Exogenous recombinant apelin increased the biologic activity of RPE cells, as well as the expression of collagen I. Apelin promoted proliferation, migration, and collagen I expression through the PI3K/Akt and MEK/Erk signaling pathways in RPE cells. From these results, we revealed the role of apelin in regulating proliferation, migration, and collagen I expression in RPE cells and the signaling mechanism under these processes, which suggested that apelin may play a profibrotic role in the development of PDR.
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spelling pubmed-38204322013-11-13 Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways Qin, Dong Zheng, Xiao-xue Jiang, Yan-rong Mol Vis Research Article PURPOSE: Our previous study showed that apelin was increased in the vitreous and fibrotic membranes of patients with proliferative diabetic retinopathy (PDR) in vivo, which suggested that apelin may be involved in the development of PDR. In this study, we investigated whether the expression of apelin was upregulated in human retinal pigment epithelial (RPE) cells in vitro under high glucose conditions. Furthermore, to explore the role of apelin in RPE cells, we investigated the effect of exogenous recombinant apelin on proliferation, migration, and collagen I (a major component of extracellular matrix molecules, associated with PDR) expression and investigated the signaling pathways involved in these processes. METHODS: Real-time PCR and western blot were performed to determine the apelin expression in ARPE-19 cells under high glucose conditions. Exogenous recombinant apelin was used to study the effect of apelin on ARPE-19 cells in vitro. Cell proliferation, migration, and collagen I expression were assessed using an MTT assay, a transwell assay, and real-time PCR analysis. LY294002 (an inhibitor of phosphatidylinositol 3-kinase) and PD98059 (an inhibitor of mitogen-activated protein kinase) were used to help to determine the apelin signaling mechanism. RESULTS: High glucose upregulated apelin expression in RPE cells. Exogenous recombinant apelin activated protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation and promoted proliferation, migration, and collagen I expression in RPE cells. Pretreatment with LY294002 and PD98059 abolished apelin-induced activation of Akt and Erk, proliferation, and collagen I expression. Apelin-induced migration was partially blocked by pretreatment with LY294002 and PD98059. CONCLUSIONS: The expression of apelin was upregulated under high glucose conditions in RPE cells in vitro. Exogenous recombinant apelin increased the biologic activity of RPE cells, as well as the expression of collagen I. Apelin promoted proliferation, migration, and collagen I expression through the PI3K/Akt and MEK/Erk signaling pathways in RPE cells. From these results, we revealed the role of apelin in regulating proliferation, migration, and collagen I expression in RPE cells and the signaling mechanism under these processes, which suggested that apelin may play a profibrotic role in the development of PDR. Molecular Vision 2013-11-07 /pmc/articles/PMC3820432/ /pubmed/24227918 Text en Copyright © 2013 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Qin, Dong
Zheng, Xiao-xue
Jiang, Yan-rong
Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways
title Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways
title_full Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways
title_fullStr Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways
title_full_unstemmed Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways
title_short Apelin-13 induces proliferation, migration, and collagen I mRNA expression in human RPE cells via PI3K/Akt and MEK/Erk signaling pathways
title_sort apelin-13 induces proliferation, migration, and collagen i mrna expression in human rpe cells via pi3k/akt and mek/erk signaling pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820432/
https://www.ncbi.nlm.nih.gov/pubmed/24227918
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