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.

Plos One
|December 10, 2016
PubMed

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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