PXD068923

PXD068923 is an original dataset announced via ProteomeXchange.

Title	UBE2S-Mediated Deubiquitination of GLUT1 via USP10 Regulates Glucose Metabolic Reprogramming and Immune Microenvironment to Promote Fibrosis in Endometriosis
Description	Abstract Background: Endometriosis (EM) is a chronic inflammatory disorder characterized by the growth of ectopic endometrial-like tissue and fibrosis. Metabolic reprogramming, particularly enhanced glycolysis, and immune microenvironment dysregulation are key features of EM progression. However, the underlying molecular mechanisms remain poorly understood. Methods: This study integrated transcriptomic analysis, immunoprecipitation-mass spectrometry (IP-MS), co-immunoprecipitation, and ubiquitination assays to systematically investigate the role of Ubiquitin-Conjugating Enzyme E2S (UBE2S) in regulating glucose metabolism and immune modulation in EM. In vitro, cell experiments, and mouse models were used to validate its effects on glycolysis, macrophage polarization, and fibrosis. Results: UBE2S was significantly upregulated in ectopic endometrial stromal cells. IP-MS analysis identified glucose transporter 1 (GLUT1) and Ubiquitin-Specific Peptidase 10 (USP10) as key interacting proteins of UBE2S. Mechanistic studies revealed that UBE2S mediates K48-linked deubiquitination of GLUT1 through USP10, stabilizing GLUT1 protein and enhancing glycolytic activity. This metabolic reprogramming leads to lactate accumulation, which induces M2 macrophage polarization and secretion of transforming growth factor β1 (TGF-β1), thereby promoting fibroblast-to-myofibroblast transition and accelerating fibrosis in the lesions. The UBE2S inhibitor cephalomannine significantly downregulated GLUT1 expression, inhibited glycolysis, blocked M2 polarization, and alleviated fibrosis in ectopic lesions. Conclusion: This study reveals the molecular mechanism by which the UBE2S–USP10–GLUT1 axis regulates the immune microenvironment and promotes fibrosis in EM through metabolic reprogramming. Our findings provide new insights into the pathogenesis of EM and offer a theoretical basis for targeting UBE2S in therapeutic strategies.
HostingRepository	iProX
AnnounceDate	2025-09-26
AnnouncementXML	Submission_2025-10-20_01:46:20.187.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Li Hu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-28 18:42:12	ID requested
⏵ 1	2025-10-20 01:46:20	announced

Dataset with its publication pending

submitter keyword: Endometriosis, UBE2S, GLUT1, USP10, Glycolysis, M2 Macrophage Polarization, Fibrosis

Guangmei Zhang
contact affiliation	Harbin Medical University
contact email	guangmeizhang@126.com
lab head
Li Hu
contact affiliation	Harbin Medical University
contact email	huli@hrbmu.edu.cn
dataset submitter

iProX dataset URI