文献类型：期刊文献

英文题名：Silencing of LOX-1 attenuates high glucose-induced ferroptosis in THVECs via the HIF-1α/SLC7A11 signaling pathway

作者：Zhang, Haiqi[1];Chang, Xinying[1];Liu, Xuan[2];Zhang, Baozhuan[2];Wang, Rongrong[1];Wang, Yuhui[1];Dai, Simeng[1];Yao, Tonghan[1];Zhang, Qi[3]

第一作者：张弘强

通信作者：Zhang, Q[1]

机构：[1]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou 730000, Peoples R China;[2]Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Peoples R China;[3]Gansu Prov Hosp, Dept Gerontol, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Gerontol, Lanzhou 730000, Peoples R China.

年份：2025

卷号：446

期号：2

外文期刊名：EXPERIMENTAL CELL RESEARCH

收录：;Scopus(收录号：2-s2.0-85219089556);WOS:【SCI-EXPANDED(收录号:WOS:001440559100001)】；

基金： Zhang Qi received support from the National Natural Science Foundation of China [81960173] and [82160166] , the Gansu Provincial Key Talent Project [2023RCXM16] , Gansu Provincial Key Research and Development Program [22YF7FA096] .

语种：英文

外文关键词：Diabetic osteoporosis; H -type vascular endothelial cells; Ferroptosis; LOX-1

摘要：Objectives: Diabetic osteoporosis (DOP) represents a significant and serious complication associated with diabetes, characterized by a complex and inadequately understood pathophysiological mechanism. Recent studies have highlighted a robust association between DOP and ferroptosis. H-type vessels play a critical role in osteoporosis, while lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with endothelial dysfunction related to diabetes. In this study, we investigate how LOX-1 affects ferroptosis in H-type vascular endothelial cells (THVECs) under high glucose (HG) conditions, aiming to elucidate the molecular mechanisms involved. Methods: THVECs were isolated from rats employing an enzymatic digestion method and subsequently validated through immunofluorescence analysis. The silencing of LOX-1 was achieved via transfection with a lentiviral vector. Cell viability was assessed using the CCK-8 assay, and ROS, MMP, GSH, MDA, and Fe2+ levels were assessed utilizing specific commercial kits. Western blotting and PCR assessed LOX-1, HIF-1 alpha, SLC7A11, and GPX4 expression levels. Results: In high glucose conditions, LOX-1 expression at both protein and mRNA levels increased, while ROS, MDA, and Fe2+ rose, and MMP and GSH levels fell, resulting in ferroptosis in THVECs. This condition could be reversed by silencing LOX-1 or by administering the ferroptosis inhibitor (Fer-1). Further analysis showed that silencing LOX-1 enhanced the expression of HIF-1 alpha, SLC7A11, and GPX4, which mitigated ferroptosis in THVECs. Conclusions: Downregulation of LOX-1 alleviates high glucose-induced ferroptosis in THVECs via the HIF-1 alpha/ SLC7A11 pathway. This suggests that LOX-1 functions as a critical target for regulating ferroptosis in THVECs, providing a novel insight into the pathological mechanisms associated with DOP.