PXD058810-1

PXD058810 is an original dataset announced via ProteomeXchange.

Title	Identification of Tie2 as a sensor for reactive oxygen species and its therapeutic implication
Description	Psoriasis is a chronic inflammatory disease characterized by hyperproliferation of keratinocytes and abnormal blood vessels. As hyperproliferation is driven by pro-inflammatory cytokines produced by activated immune cells, therapeutic strategies often target these cytokines to manage the disease. However, the role of abnormally developed blood vessels has often been overlooked in treatment approaches. In this study, we focused on blood vessels in psoriatic lesions and investigated the potential interplay between immune and endothelial cells by adopting imiquimod treated mice as in vivo model, together with various cell biological, biochemical, and structural analyses. We found that activated immune cells can generate reactive oxygen species, subsequently inducing oxidative stress in endothelial cells. Oxidative stress impairs endothelial cell layer integrity, thereby facilitating transendothelial migration of immune cells. Mechanistically, oxidative conditions inhibit Tie2 activation, potentially by modifying its cysteine residues, leading to deactivation of its vessel-stabilizing functions. Additionally, we demonstrated that reactivating Tie2 under such conditions could restore endothelial barrier function and alleviate the disease. These results suggest that Tie2 serves as a receptor that is directly responsive to oxidative environments, thereby modulating its kinase activity. Furthermore, we suggest that Tie2 reactivation is a promising alternative therapeutic approach for psoriasis.
HostingRepository	PRIDE
AnnounceDate	2025-01-28
AnnouncementXML	Submission_2025-01-28_06:28:37.497.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yongwoo Na
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-12 05:37:29	ID requested
⏵ 1	2025-01-28 06:28:37	announced

Dataset with its publication pending

submitter keyword: Human Oxidation Eclipse

Chungho Kim
contact affiliation	Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea
contact email	chungho@korea.ac.kr
lab head
Yongwoo Na
contact affiliation	Seoul National University
contact email	nyw1412@snu.ac.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058810
     1. Label: PRIDE project
     2. Name: Identification of Tie2 as a sensor for reactive oxygen species and its therapeutic implication