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

и другие.

Theranostics, Год журнала: 2024, Номер 15(3), С. 1185 - 1204

Опубликована: Дек. 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

Язык: Английский

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

и другие.

Theranostics, Год журнала: 2024, Номер 15(3), С. 1185 - 1204

Опубликована: Дек. 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

Язык: Английский

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