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Updated: Apr 9, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Published on: August 3, 2018

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FRZB-induced anti-angiogenic effect via Caveolin-1-mediated TGFβ signalling

Ching-Jou Chen1, Lei Zhou2,3, Han-Tang Chen1,4

  • 1Duke-NUS Medical School, Singapore, Singapore.

Nature Communications
|April 7, 2026
PubMed

Insights

Frizzled-related Protein (FRZB) deficiency worsens ocular angiogenesis. Therapeutic FRZB or its motif (NTR) inhibits and reverses this, offering a new treatment for sight-threatening diseases like proliferative diabetic retinopathy (PDR).

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Vascular Biology

Background:

  • Pathological neovascularization and vascular leakage drive sight-threatening eye diseases.
  • Current treatments targeting vascular endothelial growth factor (VEGF) have limitations, necessitating alternative therapies.
  • Reduced Frizzled-related Protein (FRZB) levels are observed in proliferative diabetic retinopathy (PDR).

Purpose of the Study:

  • To investigate the role of FRZB in ocular angiogenesis.
  • To evaluate the therapeutic potential of FRZB and its derivatives in preclinical models of ocular neovascularization.

Main Methods:

  • Proteomic analysis of vitreous samples from PDR patients.
  • Preclinical models of ocular angiogenesis.
  • Administration of Fc-recombinant FRZB and its netrin-related motif (Fc-NTR).
  • Assessment of additive effects with Aflibercept.
  • Mechanistic studies involving Caveolin-1 (CAV1) and TGFβ signaling pathway.

Main Results:

  • Loss of Frzb exacerbates ocular angiogenesis in preclinical models.
  • Therapeutic delivery of Fc-recombinant FRZB or Fc-NTR suppressed and reversed ocular angiogenesis.
  • Fc-NTR demonstrated additive effects with Aflibercept.
  • FRZB was found to bind CAV1, inhibit its phosphorylation, retain the TGFβ receptor ALK5, and enhance Smad2/3 signaling.

Conclusions:

  • FRZB acts as a potent endogenous suppressor of ocular angiogenesis.
  • FRZB and its derivatives represent a promising therapeutic strategy for neovascular eye diseases.
  • Targeting the FRZB-CAV1-TGFβ axis offers a novel therapeutic avenue.

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