Xinru Zheng, Qianjun Zhu, Jie Ouyang, Jing Zhang, Quanjun Liu, Jianing Fan, Peng Gao, Haijiao Long, Hong Xiang, Hongwei Lu
{"title":"PACS2/PKCα/NOX4 pathway damaged the renal vascular endothelial barrier by promoting ROS production in diabetic nephropathy mice.","authors":"Xinru Zheng, Qianjun Zhu, Jie Ouyang, Jing Zhang, Quanjun Liu, Jianing Fan, Peng Gao, Haijiao Long, Hong Xiang, Hongwei Lu","doi":"10.1007/s11010-025-05363-3","DOIUrl":null,"url":null,"abstract":"<p><p>Renal vascular endothelial barrier dysfunction plays an important role in the pathogenesis of diabetic nephropathy (DN). Reactive oxygen species (ROS) contribute to barrier dysfunction in various aspects of diabetes. Phosphofurin acidic cluster sorting protein 2 (PACS2) is related to the ROS production, but the specific signaling pathway in endothelial cells remains unclear. In this study, we explored the mechanistic function of PACS2 and its downstream PKCα/NOX4 signaling pathway in endothelial barrier damage in DN. A significant upregulation of PACS2 expression was observed in human umbilical vein endothelial cells treated with high glucose and palmitic acid and glomerular endothelial cells derived from STZ + HFD-induced DN mice. SiRNA-mediated silencing or knockdown of PACS2 reversed the impaired vascular barrier function in vivo and in vitro. Furthermore, the inhibition of PACS2 significantly downregulated the protein expression of PKCα and NOX4 protein and the production of ROS in endothelial cells. Collectively, our findings indicate that the PACS2/PKCα/NOX4 signaling pathway may participate in the pathogenesis of DN by regulating vascular endothelial barrier function.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05363-3","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Renal vascular endothelial barrier dysfunction plays an important role in the pathogenesis of diabetic nephropathy (DN). Reactive oxygen species (ROS) contribute to barrier dysfunction in various aspects of diabetes. Phosphofurin acidic cluster sorting protein 2 (PACS2) is related to the ROS production, but the specific signaling pathway in endothelial cells remains unclear. In this study, we explored the mechanistic function of PACS2 and its downstream PKCα/NOX4 signaling pathway in endothelial barrier damage in DN. A significant upregulation of PACS2 expression was observed in human umbilical vein endothelial cells treated with high glucose and palmitic acid and glomerular endothelial cells derived from STZ + HFD-induced DN mice. SiRNA-mediated silencing or knockdown of PACS2 reversed the impaired vascular barrier function in vivo and in vitro. Furthermore, the inhibition of PACS2 significantly downregulated the protein expression of PKCα and NOX4 protein and the production of ROS in endothelial cells. Collectively, our findings indicate that the PACS2/PKCα/NOX4 signaling pathway may participate in the pathogenesis of DN by regulating vascular endothelial barrier function.
期刊介绍:
Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell.
In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.