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Galectin-1 Attenuates PDGF-Mediated AKT Signaling in Retinal Pigment Epithelial Cells

Martina Bizzotto1, Annabella Ostermaier1, Caspar Liesenhoff1

  • 1Department of Ophthalmology, University Hospital, LMU Munich, Mathildenstrasse 8, 80336 Munich, Germany.

International Journal of Molecular Sciences
|September 14, 2024
PubMed

Insights

Galectin-1 reduces platelet-derived growth factor (PDGF)-mediated AKT signaling and proliferation in retinal pigment epithelial (RPE) cells. This effect is linked to decreased expression of PDGF receptor beta (PDGF-Rβ).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Ophthalmology

Background:

  • Galectins can modulate transmembrane glycoprotein functions.
  • Galectin-1 is known to interact with PDGF receptor beta (PDGF-Rβ).

Purpose of the Study:

  • To investigate the effect of galectin-1 on PDGF-BB-mediated AKT signaling and proliferation in human retinal pigment epithelial (RPE) cells.
  • To analyze the role of galectin-1 in regulating PDGF-Rβ expression and localization.

Main Methods:

  • Western blot analysis and immunohistochemical staining to assess protein expression and localization (galectin-1, PDGF-Rβ, pAKT).
  • BrdU ELISA to measure RPE cell proliferation.
  • Experiments conducted on primary human RPE cells and galectin-1-deficient immortalized RPE cells (LGALS1-/-/ARPE-19).

Main Results:

  • Galectin-1 treatment led to clustering of PDGF-Rβ and colocalization with galectin-1 in human RPE cells.
  • PDGF-BB-mediated pAKT expression was enhanced by PDGF-BB but reduced by co-incubation with galectin-1.
  • PDGF-BB-induced pAKT signaling was higher in galectin-1-deficient cells compared to wild-type.
  • Galectin-1 treatment decreased PDGF-Rβ expression in RPE cells and increased it in LGALS1-/-/ARPE-19 cells.
  • Galectin-1 significantly reduced PDGF-BB-induced RPE cell proliferation.

Conclusions:

  • Galectin-1 inhibits PDGF-mediated AKT signaling and proliferation in human RPE cells.
  • This inhibition is likely mediated by a decrease in PDGF-Rβ expression.
  • Findings highlight galectin-1's role in regulating RPE cell function relevant to ocular diseases.
Keywords:
AKT signalingARPE-19ERK signalingPDGFPDGF-Rβgalectin-1galectin-1 deficiencypAKTpERKretinal pigment epithelium cells

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