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NADPH Oxidase 1 (NOX1)-PKCdelta dependent ZO-1 phosphorylation mediates IL-33-induced inner blood-retinal barrier disruption in proliferative retinopathies.

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 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Microvascular Endothelium, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Paul Stemmer

LAB HEAD: Nikhelsh Kumar Singh

PROVIDER: PXD060282 | Pride | 2025-10-14

REPOSITORIES: Pride

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			Action	DRS
	2507_01.mzML	Mzml
	2507_01.mzid	Mzid
	2507_01.raw	Raw
	2507_02.mzML	Mzml
	2507_02.mzid	Mzid

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