Your browser doesn't support javascript.
loading
Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons.
Meng, Jie; Yang, Xiu Mei; Scheer, Oliver; Lange, Johannes; Müller, Heidi; Bürger, Susanne; Rothemund, Sven; Younis, Ruaa; Unterlauft, Jan D; Eichler, Wolfram.
Afiliación
  • Meng J; Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
  • Yang XM; Department of Ophthalmology, PLA Army General Hospital, Beijing, China.
  • Scheer O; Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
  • Lange J; Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway.
  • Müller H; Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
  • Bürger S; Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.
  • Rothemund S; Core Unit Peptide Technologies, Medical Faculty, Leipzig University, Leipzig, Germany.
  • Younis R; Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
  • Unterlauft JD; Department of Ophthalmology, University Hospital, Inselspital, Bern, Switzerland.
  • Eichler W; Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
Invest Ophthalmol Vis Sci ; 65(10): 27, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-39167401
ABSTRACT

Purpose:

The purpose of this study was to examine possible involvement of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1/Flt-1 in pigment epithelium-derived factor (PEDF)-promoted survival of retinal neurons.

Methods:

Survival of growth factor-deprived retinal ganglion cells (RGCs) and R28 cells and activation of ERK-1/-2 MAP kinases were assessed in the presence of PEDF, placental growth factor (PlGF), and VEGF using cell cultures, viability assays and quantitation of ERK-1/-2 phosphorylation. VEGFR-1/Flt-1 expression was determined using quantitative PCR (qPCR) and Western blotting. VEGFR-1/Flt-1 was knocked down in R28 cells by small interfering RNA (siRNA). Binding of a PEDF-IgG Fc fusion protein (PEDF-Fc) to retinal neurons, immobilized VEGFR-1/Flt-1 and VEGFR-1/Flt-1-derived peptides was studied using binding assays and peptide scanning.

Results:

PEDF in combination with PlGF stimulated increased cell survival and ERK-1/-2 MAP kinase activation compared to effects of either factor alone. VEGFR-1/Flt-1 expression in RGCs and R28 cells was significantly upregulated by hypoxia, VEGF, and PEDF. VEGFR-1/Flt-1 ligands (VEGF and PlGF) or soluble VEGFR-1 (sflt-1) competed with PEDF-Fc for binding to R28 cells. Depleting R28 cells of VEGFR-1/Flt-1 resulted in reduced PEDF-Fc binding when comparing VEGFR-1/Flt-1 siRNA- and control siRNA-treated cells. PEDF-Fc interacted with immobilized sflt-1, which was specifically blocked by VEGF and PlGF. PEDF-Fc binding sites were mapped to VEGFR-1/Flt-1 extracellular domains D3 and D4. Peptides corresponding to D3 and D4 specifically inhibited PEDF-Fc binding to R28 cells. These peptides and sflt-1 significantly inhibited PEDF-promoted survival of R28 cells.

Conclusions:

These results suggest that PEDF can target VEGFR-1/Flt-1 and this interaction plays a significant role in PEDF-mediated neuroprotection in the retina.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serpinas / Supervivencia Celular / Western Blotting / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Proteínas del Ojo / Factores de Crecimiento Nervioso Límite: Animals Idioma: En Revista: Invest Ophthalmol Vis Sci Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serpinas / Supervivencia Celular / Western Blotting / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Proteínas del Ojo / Factores de Crecimiento Nervioso Límite: Animals Idioma: En Revista: Invest Ophthalmol Vis Sci Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos