TFEB attenuates hyperglycemia-induced retinal capillary endothelial cells injury via autophagy regulation
TFEB attenuates hyperglycemia-induced retinal capillary endothelial cells injury via autophagy regulation
复制标题
TFEB 通过自噬调节减轻高血糖诱导的视网膜毛细血管内皮细胞损伤
DOI：
10.1002/cbin.12002
复制
发表时间：
2023
影响因子：
3.9
通讯作者：
Zhipeng You
中科院分区：
文献类型：
--
作者：
Yanhua Cheng;Huimin Fan;Kangcheng Liu;Jingying Liu;Hua Zou;Zhipeng You
糖尿病视网膜病变是糖尿病常见的微血管并发症。视网膜毛细血管内皮细胞稳态的维持需要一个完整的和不显眼的自噬流，因为它可能有助于对抗糖尿病细胞的炎症反应，细胞凋亡和氧化应激损伤。转录因子EB是自噬和溶酶体生物发生的主要调节因子，但其在糖尿病视网膜病变中的作用尚不清楚。本研究旨在证实转录因子EB在糖尿病视网膜病变中的作用，并探讨转录因子EB在体外高血糖相关内皮损伤中的作用。首先，在糖尿病视网膜组织和高糖处理的人视网膜毛细血管内皮细胞中，包括转录因子EB的核定位和自噬的表达水平降低。随后，在体外转录因子EB介导自噬。此外，转录因子EB过表达逆转了高糖诱导的自噬抑制和溶酶体功能障碍，并保护人视网膜毛细血管内皮细胞免受高糖治疗引起的炎症、凋亡和氧化应激损伤。此外，在高糖刺激下，自噬抑制剂氯喹减弱了转录因子EB过表达介导的保护作用，自噬激动剂Torin1挽救了转录因子EB敲低诱导的损伤效应。总之，这些结果表明，转录因子EB参与糖尿病视网膜病变的发展。此外，转录因子EB通过自噬保护人视网膜毛细血管内皮细胞免受高糖诱导的内皮损伤。
Diabetic retinopathy is a common microvascular complication of diabetes mellitus. The maintenance of retinal capillary endothelial cell homeostasis requires a complete and unobtrusive flow of autophagy because it may help combat the inflammatory response, apoptosis, and oxidative stress damage of cells in diabetes mellitus. The transcription factor EB is a master regulator of autophagy and lysosomal biogenesis, but its role in diabetic retinopathy remains unknown. This study aimed to confirm the involvement of transcription factor EB in diabetic retinopathy and explore the role of transcription factor EB in hyperglycemia-linked endothelial injury in vitro. First, the expression levels, including the nuclear location of transcription factor EB and autophagy, were reduced in diabetic retinal tissues and high glucose-treated human retinal capillary endothelial cells. Subsequently, autophagy was mediated by transcription factor EB in vitro. Moreover, transcription factor EB overexpression reversed high glucose-induced autophagy inhibition and lysosomal dysfunction and protected human retinal capillary endothelial cells from inflammation, apoptosis, and oxidative stress damage caused by high glucose treatment. Additionally, under high-glucose stimulation, the autophagy inhibitor chloroquine attenuated transcription factor EB overexpression-mediated protection, and the autophagy agonist Torin1 rescued transcription factor EB knockdown-induced damage effects. Taken together, these results suggest that transcription factor EB is involved in the development of diabetic retinopathy. In addition, transcription factor EB protects human retinal capillary endothelial cells from high glucose-induced endothelial damage via autophagy.