Evidence map›Paper›PMID 41060718›Full record

ArticleAmerican journal of physiology. Cell physiology2025

NADPH oxidase 1-PKCδ-dependent ZO-1 phosphorylation mediates IL-33-induced inner blood-retinal barrier disruption in proliferative retinopathies.

Geetika Kaur, Shivantika Bisen, Anamika Sharma, Nikhlesh K Singh

Abstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Geetika KaurIntegrative Biosciences Center, Wayne State University, Detroit, Michigan, United States.ORCID 0000-0003-0988-4503
Shivantika BisenIntegrative Biosciences Center, Wayne State University, Detroit, Michigan, United States.
Anamika SharmaIntegrative Biosciences Center, Wayne State University, Detroit, Michigan, United States.ORCID 0009-0004-5069-1994
Nikhlesh K SinghIntegrative Biosciences Center, Wayne State University, Detroit, Michigan, United States.ORCID 0000-0002-3665-6023

Funding

CELLULAR MECHANISMS OF PATHOLOGICAL RETINAL NEOVASCULARIZATIONR01EY029709 · NEI · WAYNE STATE UNIVERSITY · PI SINGH, NIKHLESH KUMAR · 2019 to 2023
$1.9M
HHS | NIH | National Eye Institute (NEI) EY029709NEI NIH HHS R01 EY029709Research to Prevent Blindness (RPB)
6 · The paper itself

Abstract

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 used human retinal microvascular endothelial cells (HRMVECs) and a mouse model of oxygen-induced retinopathy (OIR) to investigate the impact of interleukin-33 (IL-33) signaling on tight junction disintegration and pathological angiogenesis. Our experimental findings demonstrate that IL-33 induces zonula occludens-1 (ZO-1) serine/threonine phosphorylation and tight junction disruption in HRMVECs. In addition, mass spectroscopy analysis revealed that treating HRMVECs with IL-33 induces ZO-1 phosphorylation at the Thr861 residue. Furthermore, we observed that NOX1-PKCδ (protein kinase C-δ) 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-PKCδ-ZO-1 signaling and vascular leakage 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-PKCδ-ZO-1 signaling regulates ischemia-induced retinal endothelial cell tight junction disruption and retinal neovascularization.

Indexed as

Blood-Retinal BarrierInterleukin-33NADPH Oxidase 1Protein Kinase C-deltaZonula Occludens-1 ProteinAnimalsDisease Models, AnimalEndothelial CellsHumansMaleMiceMice, Inbred C57BLPhosphorylationRetinal NeovascularizationSignal TransductionTight JunctionsIl33 protein, mouseInterleukin-33NADPH Oxidase 1NOX1 protein, humanNOX1 protein, mouseProtein Kinase C-deltaTJP1 protein, humanTjp1 protein, mouseZonula Occludens-1 ProteinPKCδproliferative retinopathytight junctionvascular leakageZO-1

Identifiers

PMID41060718
PMCPMC12669412

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.