PXD048707

PXD048707 is an original dataset announced via ProteomeXchange.

Title	Nuclear factor 90 isoform of vascular smooth muscle cells accelerates diabetic arteriosclerotic calcification by mediating FBXW7-AGER1-AGEs axis
Description	Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the prolonged accumulation of advanced glycation end products (AGEs) induced by hyperglycemia may be closely related to the pathogenesis of aortic calcification. However, the mechanisms underlying this association remain unclear. In the current study, we investigated the role of vascular smooth muscle cell nuclear factor 90/110 (NF90/110) in mediating AGEs accumulation and accelerating diabetic atherosclerotic calcification. Using vascular smooth muscle cells (VSMCs), human samples, and mouse models, we found that hyperglycemia-mediated AGEs markedly increased VSMC NF90/110 activation both in human and mouse atherosclerotic calcified tissues with diabetes. Silencing of NF90/110 in vitro and genetic deletion of VSMC NF90/110 in mice decreased obviously AGEs-induced arteriosclerotic calcification. Mechanistically, AGEs increased the activity of NF90, which then enhanced ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase, F-box, and WD repeat domain 7 (FBXW7), thus causing the accumulation of more AGEs. Furthermore, AGEs accumulation accelerated diabetic atherosclerotic calcification by inducing VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Collectively, our study demonstrated the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic arteriosclerotic calcification. These novel findings elucidate a pivotal mechanism underlying AGE-induced diabetic atherosclerotic calcification and provide a framework for potential interventions against diabetic vascular complications.
HostingRepository	iProX
AnnounceDate	2024-01-19
AnnouncementXML	Submission_2024-04-01_23:15:03.736.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fei Xie
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	4800 Plus MALDI TOF/TOF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-19 00:59:42	ID requested
⏵ 1	2024-04-01 23:15:04	announced

Dataset with its publication pending

submitter keyword: NF90/110, diabetic calcification, advanced glycation end products, FBXW7, AGER1

Mingxiang Zhang
contact affiliation	Qilu Hospital of Shandong University
contact email	zhangmingxiang@sdu.edu.cn
lab head
Fei Xie
contact affiliation	Qilu Hospital of Shandong University
contact email	doctorxiefei2018@163.com
dataset submitter

iProX dataset URI