PXD072047-1

PXD072047 is an original dataset announced via ProteomeXchange.

Title	Interfering VE-cadherin Y685 Phosphorylation inhibits development of experimental diabetic and prediabetic retinopathy
Description	Diabetic retinopathy involves early retinal vascular barrier breakdown and pericyte loss, yet the initiating molecular events remain poorly defined. Vascular endothelial cadherin (VE-cadherin), a key regulator of endothelial integrity, is notably reduced in diabetic and prediabetic nucleoside diphosphate kinase B (NDPKB) deficient mouse retinas, particularly in the retinal deep capillary layer, and this decline precedes pericyte loss. In vitro, high glucose (HG) and NDPKB deficiency induced VE-cadherin Y685 phosphorylation, promoting its junctional internalization, activating the hexosamine biosynthesis pathway, and increasing angiopoietin 2 (Ang2), resulting in impaired endothelial barrier function and disrupting pericyte attachment. Preventing Y685 phosphorylation through VE-cadherin Y685F mutation blocked these HG- and NDPKB-driven pathological effects. Pharmacological intervention identified protein O-linked β-N-acetylglucosamin (O-GlcNAc) modification as a mediator of Y685-dependent Ang2 upregulation. In vivo, VE-cadherin Y685F knock-in mice were protected from diabetes- and prediabetes-induced vascular hyperpermeability, exhibited reduced protein O-GlcNAcylation and Ang2 induction, and maintained neuronal function. O-GlcNAc-enriched retinal proteomics further showed that the Y685F mutation restored balanced neurovascular and mitochondrial pathways. These findings highlight the potential of targeting VE-cadherin Y685 phosphorylation as a promising therapeutic approach to maintain retinal vascular integrity and attenuate pathological progression of diabetic and prediabetic retinopathy.
HostingRepository	PRIDE
AnnounceDate	2026-03-07
AnnouncementXML	Submission_2026-03-07_00:58:35.565.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuxi Feng
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	electron multiplier; Orbitrap Astral; electrospray ionization

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-16 10:08:41	ID requested
⏵ 1	2026-03-07 00:58:36	announced

Dataset with its publication pending

submitter keyword: Y685, pericyte,VE-cadherin, NDPKB, endothelial cell, metabolic, diabetic retinopathy

Yuxi Feng
contact affiliation	Experimental Pharmacology Mannheim, European Center of Angioscience, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany
contact email	yuxi.feng@medma.uni-heidelberg.de
lab head
Yuxi Feng
contact affiliation	Experimental Pharmacology Mannheim (EPM), European Center of Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
contact email	yuxi.feng@medma.uni-heidelberg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072047
     1. Label: PRIDE project
     2. Name: Interfering VE-cadherin Y685 Phosphorylation inhibits development of experimental diabetic and prediabetic retinopathy