VDR alleviates endothelial cell injury in arteriovenous fistula through inhibition of P66Shc-mediated mitochondrial ROS

• Published in: Scientific reports 2023-07, Vol.13 (1), p.11088-11088, Article 11088
• Main Authors: Han, Ya-chun, Liu, Yu-ting, Zhang, Hao, Xu, Yong, Liu, Jun, Chen, Hong, Song, Na, Qin, Dong-lu, Yang, Shikun
• Format: Article
• Language: English
• Subjects: 631/80; 692/4022; 692/420; 8-Hydroxydeoxyguanosine; Arteriovenous Fistula - metabolism; Cell injury; Constriction, Pathologic - metabolism; Endothelial cells; Fibronectin; Fistula; Fistulae; Human Umbilical Vein Endothelial Cells - metabolism; Humanities and Social Sciences; Humans; Juglone; Mitochondria; multidisciplinary; Overexpression; Pin1 protein; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Science; Science (multidisciplinary); Src Homology 2 Domain-Containing, Transforming Protein 1 - genetics; Src Homology 2 Domain-Containing, Transforming Protein 1 - metabolism; Stenosis; Transforming growth factor-b; Translocation; Umbilical vein; Vitamin D; Vitamin D receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-37510-5

To investigate the effects and mechanism of Vitamin D receptor (VDR) signaling on arteriovenous fistula (AVF) endothelial cell injury. Venous tissues of AVF stenosis patients were collected and analyzed, vascular morphology, reactive oxygen species (ROS), and the expression of VDR, P66Shc, fibronectin (FN), collagen-1 (Col-1) were detected. In addition, human umbilical vein endothelial cells (HUVECs) was used in in vitro studies. HUVECs was incubated with transforming growth factor-beta (TGF-β, 50 ng/ml). Aditionally, paricalcitol, VDR overexpression plasmid and Pin1 inhibitor Juglone were used to investigate the regulatory mechanism of VDR in mitochondrial ROS. The parameters of ROS (e.g. MitoSox) and the expression of FN, Col-1 were tested. Moreover, the mitochondrial translocation of P66Shc was analyzed. The expression of VDR was obviously decreased in the venous tissues of AVF stenosis patients. On the contrary, the expression of P66Shc, P-P66Shc, FN, Col-1 and 8-OHdG were increased significantly in the venous tissues of AVF stenosis patients ( P