OTUB2 contributes to vascular calcification in chronic kidney disease via the YAP-mediated transcription of PFKFB3 DOI Creative Commons
Yalan Li, Xiaoyue Chen, Xueqiang Xu

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 15(3), P. 1185 - 1204

Published: Dec. 31, 2024

Rationale: Chronic kidney disease (CKD) is a global public health issue, with vascular calcification (VC) being common and deadly complication.Despite its prevalence, the underlying mechanisms of VC remain unclear.In this study, we aimed to investigate whether how Otubain-2 (OTUB2) contributes VC. Methods: The relationship between OTUB2 was examined via immunohistochemical immunofluorescence staining discarded calcified radial arteries from uremic patients who underwent arteriovenous fistula operations.Additionally, mice were fed 0.2% adenine diet supplemented 1.2% phosphorus establish model CKD-related VC.Vascular smooth muscle cell (VSMC)-specific knockout overexpression performed in vivo delivery adeno-associated virus 9 vectors manipulate expression OTUB2.Additionally, VSMC established explore roles by evaluating changes osteogenic marker calcium deposition.Results: Our results revealed significant upregulation during progression.OTUB2 upregulated markers exacerbated calcification, as verified Von Kossa Alizarin red staining.Conversely, VSMC-specific deficiency significantly mitigated diet-induced CKD mice.OTUB2 knockdown or inhibition decreased Yes-associated protein (YAP) abundance.Mechanistically, bound YAP, decreasing K48-linked polyubiquitination inhibiting subsequent degradation.Knockdown YAP abolished effect on indicating YAP-mediated mechanism.Furthermore, YAP/TEAD1 complex promoter PFKFB3, increasing transcriptional activity, determined CUT&RUN-qPCR.The PFKFB3 alleviated procalcific effects OTUB2.Conclusions: findings indicate that promotes at least partially activating YAP-PFKFB3 signaling pathway.Targeting may be an appealing therapeutic strategy for

Language: Английский

Danlian-Tongmai formula improves diabetic vascular calcification by regulating CCN3/NOTCH signal axis to inhibit inflammatory reaction DOI Creative Commons
Wenting Wang, Yiwen Li, Mengmeng Zhu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Vascular calcification (VC) commonly occurs in diabetes and is associated with cardiovascular disease incidence mortality. Currently, there no drug treatment for VC. The Danlian-Tongmai formula (DLTM) a traditional Chinese medicine (TCM) prescription used diabetic VC (DVC), but its mechanisms of action remain unclear. This study aims to elucidate the effects DLTM on DVC explore underlying action. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was identify metabolites DLTM. A rat model established using streptozotocin (STZ) combined vitamin D3 (VitD3). were evaluated through alizarin red staining, calcium deposition, changes osteogenic contractile markers. specific molecular mechanism treating comprehensively analyzed by transcriptomics, docking vivo experimental verification. We identified 108 major In vivo, high-dose significantly alleviated rats. Transcriptomic analysis showed that markedly altered transcriptomic profile aortas, which regulating CCN3/NOTCH signaling pathway, promoting vascular smooth muscle contraction, inhibiting inflammatory responses. Molecular dynamics simulation demonstrated strong binding interactions between key molecules within including NOTCH1, DLL1, DLL4, hes1, hey1. experiments confirmed could upregulate CCN3, inhibit activation NOTCH ligands DLL1 downstream transcription factors hes1 hey1, reduce release cytokines IL6, IL1β, TNFα. alleviates axis Our research provides basis clinical transformation

Language: Английский

Citations

0
Exploring the effect and mechanism of action of Jinlida granules (JLD) in the treatment of diabetes-associated cognitive impairment based on network pharmacology with experimental validation DOI Creative Commons
Haiyan Gu, Yuxin Zhang,

Jinghua Sun

et al.

Annals of Medicine, Journal Year: 2024, Volume and Issue: 57(1)

Published: Dec. 26, 2024

Objectives To explore the effect and probable mechanisms of JLD in treatment type 2 diabetes mellitus (T2DM) - associated cognitive impairment (TDACI).

Language: Английский

Citations

0
OTUB2 contributes to vascular calcification in chronic kidney disease via the YAP-mediated transcription of PFKFB3 DOI Creative Commons
Yalan Li, Xiaoyue Chen, Xueqiang Xu

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 15(3), P. 1185 - 1204

Published: Dec. 31, 2024

Rationale: Chronic kidney disease (CKD) is a global public health issue, with vascular calcification (VC) being common and deadly complication.Despite its prevalence, the underlying mechanisms of VC remain unclear.In this study, we aimed to investigate whether how Otubain-2 (OTUB2) contributes VC. Methods: The relationship between OTUB2 was examined via immunohistochemical immunofluorescence staining discarded calcified radial arteries from uremic patients who underwent arteriovenous fistula operations.Additionally, mice were fed 0.2% adenine diet supplemented 1.2% phosphorus establish model CKD-related VC.Vascular smooth muscle cell (VSMC)-specific knockout overexpression performed in vivo delivery adeno-associated virus 9 vectors manipulate expression OTUB2.Additionally, VSMC established explore roles by evaluating changes osteogenic marker calcium deposition.Results: Our results revealed significant upregulation during progression.OTUB2 upregulated markers exacerbated calcification, as verified Von Kossa Alizarin red staining.Conversely, VSMC-specific deficiency significantly mitigated diet-induced CKD mice.OTUB2 knockdown or inhibition decreased Yes-associated protein (YAP) abundance.Mechanistically, bound YAP, decreasing K48-linked polyubiquitination inhibiting subsequent degradation.Knockdown YAP abolished effect on indicating YAP-mediated mechanism.Furthermore, YAP/TEAD1 complex promoter PFKFB3, increasing transcriptional activity, determined CUT&RUN-qPCR.The PFKFB3 alleviated procalcific effects OTUB2.Conclusions: findings indicate that promotes at least partially activating YAP-PFKFB3 signaling pathway.Targeting may be an appealing therapeutic strategy for

Language: Английский

Citations

0