{"title":"原花青素通过激活转录因子1表达上调滑膜拉琴1和抑制高迁移率组盒1/ toll样受体4通路缓解糖尿病视网膜病变","authors":"Limin Zheng, Yaodan Cao, Wuyun Lu, Jinqi Hao, Yanqin Yu, Songtao Yuan","doi":"10.1111/cbdd.70174","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Diabetic retinopathy (DR) remains a major cause of vision loss among working-age individuals, significantly impairing quality of life in diabetic patients. While no definitive cure exists, Procyanidin (PRO), a polyphenolic compound, has shown potential in mitigating diabetes-related complications. However, its mechanism of action in DR remains poorly understood. To explore this, we established an in vitro high glucose (HG) model using human retinal microvascular endothelial cells (hRMECs) and an in vivo diabetic rat model. Cells were cultured in normal glucose (NG, 5 mM) or HG (30 mM) for 48 h, followed by PRO treatment. Techniques including qRT-PCR, Western blotting, flow cytometry, histological staining, Transwell, tube formation, chromatin immunoprecipitation (ChIP), and dual-luciferase assays were employed. PRO treatment conferred protection against DR; however, this effect was reversed upon knockdown of activating transcription factor 1 (ATF1). Mechanistically, ATF1 enhanced transcription of synoviolin 1 (SYVN1), promoting HMGB1 degradation via ubiquitination and suppressing the HMGB1/toll-like receptor 4 (TLR4) signaling pathway. Findings from the in vitro model were validated in vivo. In conclusion, PRO alleviates DR by regulating the ATF1/SYVN1/HMGB1 axis and inhibiting pro-inflammatory signaling. These results provide novel insights into the molecular mechanism of PRO's protective role in DR and support its therapeutic potential.</p>\n </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 4","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Procyanidin Alleviates Diabetic Retinopathy by Activating the Expression of Activating Transcription Factor 1 Expression to Upregulate Synoviolin 1 and Inhibit the High Mobility Group Box 1/Toll-Like Receptor 4 Pathway\",\"authors\":\"Limin Zheng, Yaodan Cao, Wuyun Lu, Jinqi Hao, Yanqin Yu, Songtao Yuan\",\"doi\":\"10.1111/cbdd.70174\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Diabetic retinopathy (DR) remains a major cause of vision loss among working-age individuals, significantly impairing quality of life in diabetic patients. While no definitive cure exists, Procyanidin (PRO), a polyphenolic compound, has shown potential in mitigating diabetes-related complications. However, its mechanism of action in DR remains poorly understood. To explore this, we established an in vitro high glucose (HG) model using human retinal microvascular endothelial cells (hRMECs) and an in vivo diabetic rat model. Cells were cultured in normal glucose (NG, 5 mM) or HG (30 mM) for 48 h, followed by PRO treatment. Techniques including qRT-PCR, Western blotting, flow cytometry, histological staining, Transwell, tube formation, chromatin immunoprecipitation (ChIP), and dual-luciferase assays were employed. PRO treatment conferred protection against DR; however, this effect was reversed upon knockdown of activating transcription factor 1 (ATF1). Mechanistically, ATF1 enhanced transcription of synoviolin 1 (SYVN1), promoting HMGB1 degradation via ubiquitination and suppressing the HMGB1/toll-like receptor 4 (TLR4) signaling pathway. Findings from the in vitro model were validated in vivo. In conclusion, PRO alleviates DR by regulating the ATF1/SYVN1/HMGB1 axis and inhibiting pro-inflammatory signaling. These results provide novel insights into the molecular mechanism of PRO's protective role in DR and support its therapeutic potential.</p>\\n </div>\",\"PeriodicalId\":143,\"journal\":{\"name\":\"Chemical Biology & Drug Design\",\"volume\":\"106 4\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Biology & Drug Design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70174\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70174","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Procyanidin Alleviates Diabetic Retinopathy by Activating the Expression of Activating Transcription Factor 1 Expression to Upregulate Synoviolin 1 and Inhibit the High Mobility Group Box 1/Toll-Like Receptor 4 Pathway
Diabetic retinopathy (DR) remains a major cause of vision loss among working-age individuals, significantly impairing quality of life in diabetic patients. While no definitive cure exists, Procyanidin (PRO), a polyphenolic compound, has shown potential in mitigating diabetes-related complications. However, its mechanism of action in DR remains poorly understood. To explore this, we established an in vitro high glucose (HG) model using human retinal microvascular endothelial cells (hRMECs) and an in vivo diabetic rat model. Cells were cultured in normal glucose (NG, 5 mM) or HG (30 mM) for 48 h, followed by PRO treatment. Techniques including qRT-PCR, Western blotting, flow cytometry, histological staining, Transwell, tube formation, chromatin immunoprecipitation (ChIP), and dual-luciferase assays were employed. PRO treatment conferred protection against DR; however, this effect was reversed upon knockdown of activating transcription factor 1 (ATF1). Mechanistically, ATF1 enhanced transcription of synoviolin 1 (SYVN1), promoting HMGB1 degradation via ubiquitination and suppressing the HMGB1/toll-like receptor 4 (TLR4) signaling pathway. Findings from the in vitro model were validated in vivo. In conclusion, PRO alleviates DR by regulating the ATF1/SYVN1/HMGB1 axis and inhibiting pro-inflammatory signaling. These results provide novel insights into the molecular mechanism of PRO's protective role in DR and support its therapeutic potential.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.