PT - JOURNAL ARTICLE AU - Chen, Jiaqi AU - Zhang, Shuting AU - Ma, Xiaoqin AU - Chen, Aomiao AU - Wu, Yichuan AU - Wang, Geningyue AU - Zhang, Qian AU - Xue, Yaoming AU - Jia, Yijie AU - Zheng, Zongji TI - Melatonin attenuates kidney injury by alleviating lysosomal damage in diabetic kidney disease AID - 10.1101/2025.01.06.631433 DP - 2025 Jan 01 TA - bioRxiv PG - 2025.01.06.631433 4099 - http://biorxiv.org/content/early/2025/01/06/2025.01.06.631433.short 4100 - http://biorxiv.org/content/early/2025/01/06/2025.01.06.631433.full AB - Proteinuria-induced damage to renal tubular epithelial cells is one of the main causes of diabetic kidney disease (DKD), and the clearance of overloaded albumin by lysosomes is crucial for maintaining the homeostasis of renal tubular epithelial cells. Therefore, lysosomal damage is closely related to the pathogenesis of DKD, but effective prevention and treatment measures are still lacking. Melatonin (MLT) is secreted by the pineal gland and can not only regulate circadian rhythms but also maintain lysosomal homeostasis. In this study, we demonstrate the presence of significant lysosomal damage in renal tubules of DKD patients, which causes autophagy impairment and a concomitant oxidative stress imbalance; however, MLT can upregulate transcription factor EB (TFEB) to improve lysosomal damage and restore the biosynthesis in this organelle. Mechanistically, MLT may protect lysosomes via the upregulation of TFEB and the miR-205-5p‒LRP-1 pathway in renal tubules, thus improving autophagy dysfunction and oxidative imbalance in DKD.Competing Interest StatementThe authors have declared no competing interest.