PU.1 aggravates hepatic sinusoidal obstruction syndrome by upregulating PTBP1 and activating the Wnt/β-catenin pathway

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dc.contributor.authorYang, Li
dc.contributor.authorJu, Honglin
dc.contributor.authorChen, Zhiyuan
dc.contributor.authorCheng, Siqi
dc.contributor.authorLiu, Ya
dc.contributor.authorWang, Xiangyang
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2026-01-08T07:44:50Z
dc.date.available2026-01-08T07:44:50Z
dc.date.issued2026
dc.description.abstractObjective. Hepatic sinusoidal obstruction syndrome (HSOS) is a disease characterized by damage to hepatic sinusoidal endothelial cells (HSECs). This research investigates the role and regulatory pathway of PU box-binding protein (PU.1) in the progression of HSOS. Methods. We established an in vivo HSOS model through peritoneal administration of monocrotaline (MCT). Primary murine HSECs were isolated and treated with various concentrations of MCT to establish an in vitro HSOS model. PU.1 knockdown was achieved using lentiviral shRNA constructs, and its impact on oxidative stress, PTBP1 expression, β-catenin mRNA stability, and Wnt/β-catenin signaling was evaluated through kits, RT-qPCR, and western blot. Dual-luciferase and chromatin immunoprecipitation assays were conducted to assess the interaction between PU.1 and the PTBP1 promoter. The molecular association between PTBP1 and β-catenin mRNA was confirmed through RNA pull-down and RIP assays. Results. PU.1 was upregulated in MCT-induced HSOS, contributing to elevated oxidative stress and activation of the Wnt/β-catenin pathway. PU.1 directly enhanced PTBP1 transcription, which stabilized β-catenin mRNA and sustained Wnt/β-catenin signaling. PU.1 knockdown alleviated oxidative stress, reduced liver damage, and disrupted the PTBP1-β-catenin interaction, leading to Wnt/β-catenin activity inhibition. Overexpression of PTBP1 reversed the protective effects of PU.1 knockdown, reinstating oxidative stress and reactivating Wnt/β-catenin signaling. Conclusion. PU.1 facilitated HSOS pathogenesis by promoting the transcriptional activity of PTBP1 and activating the Wnt/β-catenin pathway. Targeting PU.1 can serve as a promising therapeutic strategy for reducing oxidative stress and liver damage in HSOS.
dc.formatapplication/pdf
dc.format.extent14
dc.identifier.citationHistology and Histopathology, vol.41, nº2(2026)305-318
dc.identifier.doihttps://doi.org/10.14670/HH-18-949
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/184449
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.subjectHepatic sinusoidal obstruction syndrome
dc.subjectPU.1
dc.subjectPTBP1
dc.subjectβ-catenin
dc.subjectOxidative stress
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titlePU.1 aggravates hepatic sinusoidal obstruction syndrome by upregulating PTBP1 and activating the Wnt/β-catenin pathway
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.41, Nº2, (2026)