Melatonin attenuates kidney injury by alleviating lysosomal damage in diabetic kidney disease: Melatonin delays DKD by improving lysosomal injury

TL;DR

Melatonin helps protect kidney cells in diabetic kidney disease by reducing lysosomal damage and improving cell function.

Contribution

The study reveals that melatonin alleviates lysosomal damage in diabetic kidney disease through the TFEB and miR-205-5p-LRP-1 pathways.

Findings

Significant lysosomal damage in DKD patients causes autophagy impairment and oxidative stress.

Melatonin upregulates TFEB and the miR-205-5p-LRP-1 pathway to restore lysosomal function.

Melatonin improves autophagy dysfunction and oxidative imbalance in diabetic kidney disease.

Abstract

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 the 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 of 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.

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