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Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1018-1027页

作者： Yu-Sheng Zhu Si-Rui Zhou Hui-Hui Zhang Tong Wang Xiao-Dong Chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

关键词： erlotinib epidermal growth factor receptor protein kinase B epithelial-mesenchymal transition retinal pigment epithelium cell

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Expression of adenosine receptors in human retinal pigment epithelium cells in vitro

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Chinese Medical Journal 2011年第8期124卷 1139-1144页

作者： WAN Wen-juan CUI Dong-mei YANG Xiao HU Jian-min LI Chuan-xu HU Shou-long Klaus Trier ZENG Jun-wen State Key Laboratory of Ophthalmology Zhongshan OphthalmicCenter Sun Yat-sen University Guangzhou Guangdong 510060China

Background Adenosine receptors （ADORs） have been reported to play a role in experimental myopia. This study aimed to determine the distribution of ADORs in human retinal pigment epithelium （RPE） cells cultured in vitro.Methods Human RPE cells （cell line D407） were cultured in vitro. ADOR mRNA in RPE was detected by reverse transcription polymerase chain reaction. ADOR protein expression in RPE was confirmed by Western blotting analysis of cell lysates. Confocal fluorescence microscopy was used to study the subcellular distribution of ADORs.Results All four subtypes of ADORs mRNA and protein were expressed in human RPE. This was confirmed by Western blotting analysis. The ADOR subtypes were differently distributed within the cells. ADORA1 was expressed in nucleus, perinucleus and cytoplasm of RPE. ADORA2A was concentrated mainly in one side of the perinucleus and cytoplasm of RPE. ADORA2B was strongly expressed in the nucleus, perinucleus and the cytoplasm, and ADORA3 was expressed weakly in the cytoplasm of RPE.Conclusions ADORs are expressed in human RPE. The different distribution at the subcellular level suggests different functions of ADOR subtypes.

关键词： retinal pigment epithelium cell adenosine receptors cell culture

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Eliminating residual iPS cells for safety in clinical application

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Protein & cell 2015年第7期6卷 469-471页

作者： Shigeo Masuda Shigeru Miyagawa Satsuki Fukushima Nagako Sougawa Kaori Okimoto Chika Tada Atsuhiro Saito Yoshiki Sawa Department of Cardiovascular Surgery Osaka University Graduate School of Medicine Osaka 565-0871 Japan

First-in-human clinical trial for age-related macular degen- eration using iPSC-derived retinal pigment epithelium （RPE） cells was conducted in 2014, showing no serious adverse effects to date, including tumor formation. This appears to be attributable to relatively small number of transplanted cells, and distinct morphology of RPE cells; it might be relatively easy to minimize contamination of undifferentiated cells. However,

关键词： retinal pigment epithelium Teratoma Macular Degeneration retinal pigment epithelium cell Undifferentiated cell

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