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YM155 inhibits retinal pigment epithelium cell survival through EGFR/MAPK signaling pathway
Teng Li1,2,3,4, Hong-Bing Zhang1,2,3,4, Jia-Min Meng1,2
1First Affiliated Hospital of Northwest University, Northwest University, Xi'an 710069, Shaanxi Province, China.
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.
Insights
YM155 reduces retinal pigment epithelium cell survival and migration by affecting the epidermal growth factor receptor (EGFR)/MAPK pathway. This suggests YM155
Area of Science:
- Cell Biology
- Molecular Biology
- Ophthalmology
Background:
- Retinal pigment epithelium (RPE) cells play a crucial role in retinal health.
- Dysregulation of RPE cell survival and migration is implicated in proliferative vitreoretinopathy.
- Understanding the molecular mechanisms governing RPE cell behavior is vital for therapeutic development.
Purpose of the Study:
- To investigate the effects of YM155 on the viability and function of human immortalized RPE cells (ARPE-19).
- To elucidate the underlying regulatory mechanisms, particularly the epidermal growth factor receptor (EGFR)/MAPK signaling pathway.
Main Methods:
- ARPE-19 cells were treated with YM155 and epidermal growth factor (EGF).
- Cell viability, apoptosis, proliferation, and migration were assessed using MTT, flow cytometry, BrdU incorporation, and wound-healing assays, respectively.
- EGFR/MAPK pathway proteins and EGFR localization were analyzed via immunoblotting and immunofluorescence.
Main Results:
- YM155 suppressed ARPE-19 cell viability, proliferation, and migration in a dose- and time-dependent manner, inducing minimal cell death.
- YM155 modulated EGFR/MAPK signaling by down-regulating total EGFR and phosphorylated ERK, while up-regulating phosphorylated P38MAPK and JNK.
- YM155 induced EGFR endocytosis and attenuated EGF-stimulated RPE cell proliferation and migration, decreasing phosphorylated EGFR and ERK expression.
Conclusions:
- YM155 inhibits RPE cell survival, proliferation, and migration, primarily through the EGFR/MAPK signaling pathway.
- The observed effects involve modulation of EGFR activity and downstream signaling components.
- YM155 shows potential as a therapeutic agent for preventing and treating abnormal RPE cell behavior in proliferative vitreoretinopathy.
