YM155 inhibits retinal pigment epithelium cell survival through EGFR/MAPK signaling pathway |
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| Authors: | Teng Li Hong-Bing Zhang Jia-Min Meng Bo Yuan Wen-Juan Lin Yue Feng Xiao-Dong Chen |
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| Affiliation: | First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China; Department of Ophthalmology, Xi''an No.1 Hospital, Xi''an 710002, Shaanxi Province, China; Shaanxi Institute of Ophthalmology, Shaanxi Provincial Key Lab of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, Xi''an 710002, Shaanxi Province, China,First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China; Department of Ophthalmology, Xi''an No.1 Hospital, Xi''an 710002, Shaanxi Province, China; Shaanxi Institute of Ophthalmology, Shaanxi Provincial Key Lab of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, Xi''an 710002, Shaanxi Province, China,First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China,First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China,First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China,First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China and First Affiliated Hospital of Northwest University, Northwest University, Xi''an 710069, Shaanxi Province, China; College of Life Sciences, Northwest University, Xi''an 710069, Shaanxi Province, China; Department of Ophthalmology, Xi''an No.1 Hospital, Xi''an 710002, Shaanxi Province, China; Shaanxi Institute of Ophthalmology, Shaanxi Provincial Key Lab of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, Xi''an 710002, Shaanxi Province, China |
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| Abstract: | ![]()
AIM: To investigate YM155''s effect on retinal pigment epithelium (RPE) cells'' viability and the potential regulatory mechanisms.METHODS: Human immortalized RPE cell lines (ARPE-19 cell line) were processed with YM155 and epidermal growth factor (EGF). ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay, and apoptosis was tested by flow cytometry assay. ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay, and migration ability was evaluated via a wound-healing assay. Epidermal growth factor receptor (EGFR)/MAPK pathway proteins were tested via immunoblotting. EGFR localization was examined by immunofluorescence assay.RESULTS: YM155 suppressed ARPE-19 cells'' viability in a time and concentration-dependent manner. A high dose of YM155 caused a small amount of ARPE-19 cell death. YM155 significantly diminished the ARPE-19 cells'' proliferative and migrative capacity. YM155 down-regulated total EGFR and phosphorylated external signal-regulated protein kinase (ERK), and it up-regulated the phosphorylation of P38MAPK and c-Jun N-terminal kinase (JNK). YM155 induced endocytosis of EGFR in ARPE-19 cell. YM155 also attenuated EGF-induced ARPE-19 cells'' proliferative and migrative capacity. Moreover, YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF.CONCLUSION: YM155 inhibits RPE cell survival, the cell proliferative and migrative capacity, and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway. YM155 might, therefore, be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy. |
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| Keywords: | YM155 retinal pigment epithelial cell epidermal growth factor receptor mitogen-activated protein kinase |
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