PXD073342

PXD073342 is an original dataset announced via ProteomeXchange.

Title	Phospho-proteomics study on FRZB-treated human retinal microvascular endothelial cells (HRECs)
Description	Pathological neovascularization and vascular leakage are central drivers of many sight- threatening diseases. While strategies targeting vascular endothelial growth factor (VEGF) have transformed clinical outcomes, a substantial proportion of patients do not benefit from the treatment, partially attributed to compensatory activation of alternative angiogenic pathways. Two independent vitreous proteomics studies in patients with proliferative diabetic retinopathy (PDR) revealed a significant reduction in the level of Frizzled-related Protein (FRZB), a finding mirrored in preclinical models of ocular angiogenesis. Loss of Frzb in mice exacerbated ocular angiogenesis, while therapeutic delivery of Fc-FRZB recombination protein or its functional domain netrin-related motif (NTR) potently suppressed and reversed ocular angiogenesis across various preclinical models. Notably, Fc-NTR synergized with Aflibercept, suggesting its potential as a combination therapy. Mechanistically, FRZB doesn’t modulate Wnt signalling in retinal microvascular endothelial cells. Instead, it binds directly to Caveolin-1 (CAV1), inhibits its phosphorylation, promotes surface retention of the TGFβ type I receptor ALK5, and ultimately leads to cytoplasmic accumulation of phosphorylated Smad2/3. Intriguingly, retinal endothelial cells expressing a phosphomimetic CAV1 mutant (Y42D) at a previously uncharacterized site, Tyr42, were resistant to FRZB’s anti-angiogenic effects, establishing a novel CAV1–TGFβ signalling axis as the molecular basis of FRZB’s action. Collectively, these findings define FRZB as a novel suppressor of ocular angiogenesis, uncover a previously unknown mechanism of TGFβ regulation, and establish Fc-NTR as a promising therapeutic candidate for treating ocular angiogenic diseases.
HostingRepository	PRIDE
AnnounceDate	2026-03-13
AnnouncementXML	Submission_2026-03-12_21:14:27.068.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lei Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-21 05:42:22	ID requested
⏵ 1	2026-03-12 21:14:27	announced

Dataset with its publication pending

submitter keyword: FRZB,Phospho-proteomics, human retinal microvascular endothelial cells

Lei ZHOU
contact affiliation	School of Optometry, The Hong Kong Polytechnic University
contact email	zhou.lei.seri@gmail.com
lab head
Lei Zhou
contact affiliation	The Hong Kong Polytechnic University
contact email	zhou.lei.seri@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073342
     1. Label: PRIDE project
     2. Name: Phospho-proteomics study on FRZB-treated human retinal microvascular endothelial cells (HRECs)