PXD060282-1

PXD060282 is an original dataset announced via ProteomeXchange.

Title	NADPH Oxidase 1 (NOX1)-PKCdelta dependent ZO-1 phosphorylation mediates IL-33-induced inner blood-retinal barrier disruption in proliferative retinopathies.
Description	Proliferative retinopathies are associated with abnormal angiogenesis that can result in visual impairment or vision loss. The tight junction complex regulates blood-retinal barrier integrity; however, its role in proliferative retinopathies is still at an early stage. Here, we employed human retinal endothelial cells (HRMVECs), and a mouse model of oxygen-induced retinopathy (OIR) to investigate the impact of IL-33 signaling on tight junction disintegration and pathological angiogenesis. Our experimental findings demonstrate that IL-33 induces ZO-1 serine/threonine phosphorylation and tight junction disruption in HRMVECs. In addition, mass-spectroscopy (MS) analysis revealed that treating of HRMVECs with IL-33 induces ZO-1 phosphorylation at Thr861 residue. Furthermore, we observed that NOX1-PKC- signaling modulates IL-33-induced ZO-1 phosphorylation and tight junction integrity in HRMVECs. We also observed that IL-33 depletion significantly reduces OIR-induced NOX1-PKC-ZO-1 signaling, vascular leakage, and pathological retinal neovascularization in the ischemic retina. We also observed that the NOX1-specific inhibitor, fluoflavine (ML-090), attenuated OIR-induced NADPH oxidase activity and pathological retinal neovascularization in the ischemic retina. Thus, we infer that IL-33-mediated NOX1-PKC-ZO-1 signaling regulates ischemia-induced retinal endothelial cell tight junction disruption and retinal neovascularization.
HostingRepository	PRIDE
AnnounceDate	2025-10-14
AnnouncementXML	Submission_2025-10-14_09:07:55.074.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD060282
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Stemmer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-28 06:49:16	ID requested
⏵ 1	2025-10-14 09:07:55	announced

10.1152/AJPCELL.00308.2025;

10.6019/PXD060282;

submitter keyword: Tight junction

ZO-1

PKC delta

proliferative retinopathy

vascular leakage

Nikhelsh Kumar Singh
contact affiliation	Dept. of Ophthalmology, Visual and Anatomical Sciences Wayne State University School of Medicine
contact email	nsingh2@wayne.edu
lab head
Paul Stemmer
contact affiliation	Wayne State University
contact email	pmstemmer@wayne.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060282
     1. Label: PRIDE project
     2. Name: NADPH Oxidase 1 (NOX1)-PKCdelta dependent ZO-1 phosphorylation mediates IL-33-induced inner blood-retinal barrier disruption in proliferative retinopathies.