دورية أكاديمية
Endothelial β-catenin upregulation and Y142 phosphorylation drive diabetic angiogenesis via upregulating KDR/HDAC9
| العنوان: | Endothelial β-catenin upregulation and Y142 phosphorylation drive diabetic angiogenesis via upregulating KDR/HDAC9 |
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| المؤلفون: | Zhenfeng Chen, Bingqi Lin, Xiaodan Yao, Jie Weng, Jinlian Liu, Qi He, Ke Song, Chuyu Zhou, Zirui Zuo, Xiaoxia Huang, Zhuanhua Liu, Qiaobing Huang, Qiulin Xu, Xiaohua Guo |
| المصدر: | Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-22 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Cytology |
| مصطلحات موضوعية: | Diabetic angiogenesis, Advanced glycation end products, β-catenin, Phosphorylation, KDR, HDAC9, Medicine, Cytology, QH573-671 |
| الوصف: | Abstract Background Diabetic angiogenesis is closely associated with disabilities and death caused by diabetic microvascular complications. Advanced glycation end products (AGEs) are abnormally accumulated in diabetic patients and are a key pathogenic factor for diabetic angiogenesis. The present study focuses on understanding the mechanisms underlying diabetic angiogenesis and identifying therapeutic targets based on these mechanisms. Methods In this study, AGE-induced angiogenesis serves as a model to investigate the mechanisms underlying diabetic angiogensis. Mouse aortic rings, matrigel plugs, and HUVECs or 293T cells were employed as research objects to explore this pathological process by using transcriptomics, gene promoter reporter assays, virtual screening and so on. Results Here, we found that AGEs activated Wnt/β-catenin signaling pathway and enhanced the β-catenin protein level by affecting the expression of β-catenin degradation-related genes, such as FZDs (Frizzled receptors), LRPs (LDL Receptor Related Proteins), and AXIN1. AGEs could also mediate β-catenin Y142 phosphorylation through VEGFR1 isoform5. These dual effects of AGEs elevated the nuclear translocation of β-catenin and sequentially induced the expression of KDR (Kinase Insert Domain Receptor) and HDAC9 (Histone Deacetylase 9) by POU5F1 and NANOG, respectively, thus mediating angiogenesis. Finally, through virtual screening, Bioymifi, an inhibitor that blocks VEGFR1 isoform5-β-catenin complex interaction and alleviates AGE-induced angiogenesis, was identified. Conclusion Collectively, this study offers insight into the pathophysiological functions of β-catenin in diabetic angiogenesis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1478-811X |
| Relation: | https://doaj.org/toc/1478-811X |
| DOI: | 10.1186/s12964-024-01566-1 |
| URL الوصول: | https://doaj.org/article/39986a6a01c2437c888ae0c46e26452b |
| رقم الأكسشن: | edsdoj.39986a6a01c2437c888ae0c46e26452b |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/s12964-024-01566-1 |