PXD075726

PXD075726 is an original dataset announced via ProteomeXchange.

Title	Endothelial CDC42 deficiency aggravates pulmonary fibrosis via the PPARα-mediated lipid accumulation and cellular dysfunction in systemic sclerosis
Description	Systemic sclerosis (SSc) is an autoimmune disease that causes vascular lesions and fibrosis in several organs, including the skin and lungs. Currently, therapy options for SSc-associated interstitial lung disease (SSc-ILD) are limited. Endothelial cells, notably their proliferation and migratory capacities, play an important role in angiogenesis and tissue regeneration. Cell Division Cycle 42 (CDC42), a member of the small GTPase family, regulates cell cycle and metabolism. However, its function and mechanism in SSc-ILD remain unknown. We found that decreased CDC42 expression in endothelial cells is a common feature in human patients with SSc-ILD and in bleomycin (BLM)-induced SSc mouse model. CDC42 deficiency increased BLM-induced endothelial lipid accumulation and endothelial dysfunction, aggravating pulmonary fibrosis. Conversely, endothelial cell-specific overexpression of Cdc42 effectively improved pulmonary vascular permeability and reduced fibrosis in mice. Mechanistically, Cdc42 directly binds Signal Transduction and Activation Factor 3 (STAT3), reducing its nuclear translocation and thereby inhibiting Peroxisome Proliferator-Activated Receptor Alpha (PPARα) and Fatty Acid Binding Protein 4 (FABP4) transcription and expression, which improves lipid accumulation and endothelial cell function. This study demonstrates that Cdc42 deficiency exacerbates BLM-induced endothelial lipid accumulation and dysfunction by regulating the STAT3-PPARα-FABP4 axis, thereby worsening pulmonary fibrosis. Targeting this signaling axis offers a novel perspective and potential intervention strategy for SSc-ILD treatment.
HostingRepository	iProX
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-17_00:29:48.019.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pei Liu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-17 00:24:53	ID requested
⏵ 1	2026-03-17 00:29:48	announced

Dataset with its publication pending

submitter keyword: Systemic sclerosis, lung fibrosis, endothelial cell, CDC42, lipid metabolism

Guodong Hu
contact affiliation	Southern Medical University
contact email	1390442861@qq.com
lab head
Pei Liu
contact affiliation	Southern Medical University
contact email	isliupei@163.com
dataset submitter

iProX dataset URI