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VEGFR2 and VEGF-C Suppresses the Epithelial-Mesenchymal Transition Via YAP in Retinal Pigment Epithelial Cells

Y Du1, Q Chen1, L Huang1

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

Current Molecular Medicine
|October 6, 2018
PubMed
Abstract

Insights

Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and VEGF-C play crucial roles in maintaining retinal pigment epithelial (RPE) cell function. Their loss triggers epithelial-mesenchymal transition (EMT) by activating the YAP pathway.

Area of Science:

  • Ophthalmology and cell biology research.
  • Focus on retinal pigment epithelial (RPE) cell signaling.

Background:

  • Retinal pigment epithelial (RPE) cells secrete VEGF-A and VEGFR2, but autocrine VEGF signaling functions are unclear.
  • Anti-VEGF therapies are standard for ocular vascular diseases, necessitating understanding of VEGF roles in RPE.

Purpose of the Study:

  • To elucidate the functions of VEGF signaling within RPE cells.
  • To evaluate the consequences of interrupting VEGF signaling in RPE cells.

Main Methods:

  • siRNA-mediated knockdown of VEGF and Hippo pathway genes in RPE cells.
  • Adenovirus-mediated overexpression of VEGFR2.
  • Analysis of epithelial-mesenchymal transition (EMT) markers and YAP downstream genes via qPCR and Western Blot.
  • Immunofluorescence staining for tissue and mouse samples.

Main Results:

  • VEGFR2 knockdown induced EMT in RPE cells, both in vitro and in vivo.
  • VEGF-C loss, not VEGF-A loss, triggered EMT.
  • VEGFR2 ablation-induced EMT was mediated by YAP activation, an effector of the Hippo pathway.
  • Human proliferative vitreoretinopathy (PVR) membranes showed an inverse correlation between VEGFR2 and YAP expression.

Conclusions:

  • VEGFR2 and VEGF-C have novel roles in RPE cell EMT and the Hippo pathway.
  • VEGFR2 and VEGF-C are essential for maintaining the normal physiological state of RPE cells.
Keywords:
Hippo pathwayRetinal pigment epithelial cellVEGFR2epithelial-mesenchymal transitioneyevascular endothelial growth factoryes-associated protein.

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