Publication:
UCHL1 enhances TSC1 transcription by stabilizing FOXO1 through deubiquitination in knee osteoarthritis

Simple item page
dc.contributor.authorJiawei Lu
dc.contributor.authorChonghao Gu
dc.contributor.authorZikang Xie
dc.contributor.authorZhongyu Xia
dc.contributor.authorBingqing Guo
dc.contributor.authorTao Jiang
dc.contributor.authorYu Wang
dc.contributor.departmentBiología Celular e Histología
dc.contributor.editorUniversidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.date.accessioned2026-05-07T11:35:40Z
dc.date.available2026-05-07T11:35:40Z
dc.date.issued2026
dc.description.abstractFerroptosis has been shown to play a significant role in the pathophysiological progression of knee osteoarthritis (KOA). In this study, we sought to investigate the biological role of Ubiquitin C-terminal hydrolase 1 (UCHL1) in KOA and elucidate its underlying molecular mechanisms. An in vitro KOA cell model was established by stimulating C28/I2 chondrocytes with IL-1β, and UCHL1 expression was decreased in IL-1β-treated chondrocytes. Notably, overexpression of UCHL1 significantly alleviated IL-1β induced ferroptosis and extracellular matrix (ECM) degradation. Mechanistically, UCHL1 facilitated the deubiquitination and stabilization of FOXO1. Knockdown of FOXO1 partially reversed the inhibitory effects of UCHL1 on ferroptosis and ECM degradation. Furthermore, FOXO1 was found to bind to the Tuberous Sclerosis Complex 1 (TSC1) promoter, enhancing TSC1 transcription. Intriguingly, knockdown of FOXO1 counteracted the inhibitory effects of UCHL1 overexpression on ferroptosis and ECM degradation, while these effects were rescued by TSC1 overe xpression. In vivo experiments demonstrated that UCHL1 alleviated cartilage damage in KOA rats by inhibiting ferroptosis and ECM degradation through the FOXO1/TSC1 axis. These findings demonstrate the pivotal role of UCHL1 in regulating ferroptosis and maintaining ECM homeostasis, offering novel insights into the molecular mechanisms driving KOA progression.
dc.formatapplication/pdf
dc.format.extent16
dc.identifier.doihttps://doi.org/10.14670/HH-18-995
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/230521
dc.languageeng
dc.relationSin financiación externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectFOXO1
dc.subjectTSC1
dc.subjectDeubiquitination
dc.subjectKnee osteoarthritis
dc.subjectUCHL1
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleUCHL1 enhances TSC1 transcription by stabilizing FOXO1 through deubiquitination in knee osteoarthritis
dc.typeinfo:eu-repo/semantics/article
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Wang-41-863-878-2026 (2).pdf
Size:
34.18 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
license.txt
Size:
1.37 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Thumbnail Image
Name:
Wang-41-863-878-2026 (2).pdf
Size:
34.18 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Histology and histopathology, Vol.41, Nº5, (2026)