Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway

Purpose. Recent research has provided novel insight into the function of fibromodulin (FMOD) in wound healing and angiogenesis. The role of FMOD in initiation of proliferative vitreoretinopathy (PVR) has not been studied. This study investigated the effect of FMOD on human retinal pigment epithelial...

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Main Authors: He Hu, Shanshan Li, Jianqiao Li, Chao Huang, Fang Zhou, Li Zhao, Wenzhen Yu, Xiao Qin
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Ophthalmology
Online Access:http://dx.doi.org/10.1155/2018/5708537
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author He Hu
Shanshan Li
Jianqiao Li
Chao Huang
Fang Zhou
Li Zhao
Wenzhen Yu
Xiao Qin
author_facet He Hu
Shanshan Li
Jianqiao Li
Chao Huang
Fang Zhou
Li Zhao
Wenzhen Yu
Xiao Qin
author_sort He Hu
collection DOAJ
description Purpose. Recent research has provided novel insight into the function of fibromodulin (FMOD) in wound healing and angiogenesis. The role of FMOD in initiation of proliferative vitreoretinopathy (PVR) has not been studied. This study investigated the effect of FMOD on human retinal pigment epithelial (RPE) cell, which plays an essential role in the progression of PVR, and the possible mechanisms. Methods. Small interfering (si) RNA-based gene transfer technology was used to decrease FMOD expression and to study its effects on RPEs in vitro. Cell Counting Kit-8 assays, transwells, and flow cytometry analysis were used to measure cell proliferation, migration, cell cycle, and apoptosis. Western blot was used to measure expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), extracellular signal-related kinase 1/2 (ERK1/2), and phosphoinositide 3 kinase (PI3K/AKT). Results. After transfection of RPEs with a FMOD-specific siRNA, cell proliferation and migration were inhibited to the percentage of 65% ± 5% and 39% ± 10%, respectively, compared to the control group. Depletion of FMOD induced cell cycle arrest and apoptosis in RPE cells. Downregulation of VEGF, VEGFR2, and phosphorylated AKT (p-AKT) were detected in transfected RPEs. Conclusion. Depletion of FMOD selectively downregulated the expression of VEGF and VEGFR2 and inhibited the signaling pathway of AKT phosphorylation, which consequently inhibited the proliferation and migration of RPE Cell.
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spelling doaj-art-938e9b99e9904bd8a7e5d48d7f4a1c272025-02-03T01:21:08ZengWileyJournal of Ophthalmology2090-004X2090-00582018-01-01201810.1155/2018/57085375708537Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT PathwayHe Hu0Shanshan Li1Jianqiao Li2Chao Huang3Fang Zhou4Li Zhao5Wenzhen Yu6Xiao Qin7Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, ChinaDepartment of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Blood Transfusion, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Ophthalmology, Peking University People’s Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, ChinaDepartment of Ophthalmology, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, ChinaPurpose. Recent research has provided novel insight into the function of fibromodulin (FMOD) in wound healing and angiogenesis. The role of FMOD in initiation of proliferative vitreoretinopathy (PVR) has not been studied. This study investigated the effect of FMOD on human retinal pigment epithelial (RPE) cell, which plays an essential role in the progression of PVR, and the possible mechanisms. Methods. Small interfering (si) RNA-based gene transfer technology was used to decrease FMOD expression and to study its effects on RPEs in vitro. Cell Counting Kit-8 assays, transwells, and flow cytometry analysis were used to measure cell proliferation, migration, cell cycle, and apoptosis. Western blot was used to measure expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), extracellular signal-related kinase 1/2 (ERK1/2), and phosphoinositide 3 kinase (PI3K/AKT). Results. After transfection of RPEs with a FMOD-specific siRNA, cell proliferation and migration were inhibited to the percentage of 65% ± 5% and 39% ± 10%, respectively, compared to the control group. Depletion of FMOD induced cell cycle arrest and apoptosis in RPE cells. Downregulation of VEGF, VEGFR2, and phosphorylated AKT (p-AKT) were detected in transfected RPEs. Conclusion. Depletion of FMOD selectively downregulated the expression of VEGF and VEGFR2 and inhibited the signaling pathway of AKT phosphorylation, which consequently inhibited the proliferation and migration of RPE Cell.http://dx.doi.org/10.1155/2018/5708537
spellingShingle He Hu
Shanshan Li
Jianqiao Li
Chao Huang
Fang Zhou
Li Zhao
Wenzhen Yu
Xiao Qin
Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway
Journal of Ophthalmology
title Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway
title_full Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway
title_fullStr Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway
title_full_unstemmed Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway
title_short Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway
title_sort knockdown of fibromodulin inhibits proliferation and migration of rpe cell via the vegfr2 akt pathway
url http://dx.doi.org/10.1155/2018/5708537
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