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MicroRNA-182 Suppresses HGF/SF-Induced Increases in Retinal Pigment Epithelial Cell Proliferation and Migration
Lihua Wang1,2, Feng Dong3, Peter S Reinach1,2
1School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Abstract:
As increases in hepatocyte growth factor/scatter factor (HGF/SF) induce retinal pigment epithelial (RPE) migration and proliferation into the vitreous cavity and contribute to proliferative vitreoretinopathy (PVR) development, we determined if changes in miR-182 expression affect such behavioral changes. We found that miR-182 expression was less in PVR clinical samples than in primary RPE cells whereas c-Met was upregulated. Ectopic miR-182 inhibited RPE cell proliferation, cell cycle, and migration. Bioinformatic analysis identified c-Met as a miR-182 target, which was confirmed with the luciferase reporter assay. Transfection of miR-182 into RPE cells induced c-Met downregulation, which led to reduced cell proliferation and migration through declines in p-Akt formation. MiR-182 downregulation along with c-Met upregulation in PVR tissues suggest that these two opposing effects play important roles in PVR development. As ectopic miR-182 expression suppressed RPE cell proliferation and migration, strategies to selectively upregulate miR-182 expression in a clinical setting may provide a novel option to treat this disease.
Insights
MicroRNA-182 (miR-182) downregulation and c-Met upregulation are linked to proliferative vitreoretinopathy (PVR). Restoring miR-182 inhibits RPE cell proliferation and migration, offering a potential PVR treatment strategy.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- Hepatocyte growth factor/scatter factor (HGF/SF) drives retinal pigment epithelial (RPE) cell changes contributing to proliferative vitreoretinopathy (PVR).
- The role of microRNA-182 (miR-182) in PVR pathogenesis is not well understood.
Purpose of the Study:
- To investigate the relationship between miR-182 expression and PVR.
- To determine if miR-182 affects RPE cell behavior relevant to PVR development.
Main Methods:
- Comparative analysis of miR-182 and c-Met expression in PVR samples versus primary RPE cells.
- In vitro experiments involving ectopic miR-182 transfection into RPE cells.
- Bioinformatic analysis and luciferase reporter assays to identify miR-182 targets.
- Assessment of RPE cell proliferation, cell cycle, and migration.
- Western blot analysis to evaluate signaling pathway activation (p-Akt).
Main Results:
- miR-182 expression was significantly lower in PVR samples compared to primary RPE cells, with concurrent upregulation of c-Met.
- Ectopic miR-182 expression suppressed RPE cell proliferation, cell cycle progression, and migration.
- c-Met was confirmed as a direct target of miR-182.
- miR-182-induced c-Met downregulation led to reduced RPE cell proliferation and migration via decreased p-Akt signaling.
Conclusions:
- The inverse correlation between miR-182 and c-Met in PVR suggests their opposing roles in disease development.
- Upregulating miR-182 effectively inhibits key RPE cell behaviors implicated in PVR.
- Targeted upregulation of miR-182 presents a potential novel therapeutic strategy for PVR.
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