Salidroside and FG-4592 ameliorate high glucose-induced glomerular endothelial cells injury via HIF upregulation

• Published in: Biomedicine & pharmacotherapy Vol. 118; p. 109175
• Main Authors: Xie, Rui-yan, Fang, Xue-ling, Zheng, Xiao-bin, Lv, Wei-ze, Li, Yi-jie, Ibrahim Rage, Hamze, He, Qiao-lan, Zhu, Wei-ping, Cui, Tong-xia
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2019; Elsevier
• Subjects: Animals; Apoptosis - drug effects; Basic Helix-Loop-Helix Transcription Factors - biosynthesis; Cell Survival - drug effects; Cells, Cultured; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - pathology; FG-4592; Glucose - toxicity; Glucosides - administration & dosage; Glucosides - pharmacology; Glycine - administration & dosage; Glycine - analogs & derivatives; Glycine - pharmacology; HIF-1α; HIF-2α; High glucose; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; Isoquinolines - administration & dosage; Isoquinolines - pharmacology; Kidney Glomerulus - drug effects; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Phenols - administration & dosage; Phenols - pharmacology; Protein Stability; Rats; Salidroside; Up-Regulation; Salidroside; FG-4592; HIF-1α; HIF-2α; High glucose
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109175

[Display omitted] Increasing research indicates that hyperglycemia plays a crucial role in the progression of diabetic nephropathy (DN); however, effective treatment for preventing or slowing DN progression are seriously lacking. Although salidroside (SAL) has been demonstrated to have a positive anti-diabetic effect, the cellular mechanisms remain unclear. FG-4592, a novel prolyl hydroxylase inhibitor, was used to regulate HIF-1α and HIF-2α expression. The present study aimed to explore the underlying mechanisms of SAL and FG-4592 on high glucose (HG)-induced rat glomerular endothelial cells (rGECs) injury. HG-cultured rGECs were used to induce a diabetic environment. An MTT assay, RT-qPCR, Western blot, flow cytometry, and immunofluorescent staining were performed to investigate the effects of SAL on HG-induced rGECs injury. FG-4592 and SAL protected rGECs against HG-induced injury by increasing cellular viability and reducing the cell apoptosis rate. SAL and FG-4592 downregulated PHD-2 expression and upregulated HIF-1α and HIF-2α expression. In conclusion, our findings suggest that SAL and FG-4592 ameliorate HG-induced rGEC injury by upregulating HIF expression, indicating that SAL and FG-4592 might be favorable for further DN-treatment.