Work

Melatonin Alleviates Albumin-Induced Tubular Cell Injury by Activating Clock-Controlled Nuclear Enriched Abundant Transcript 1-Mediated Proliferation

Year: 2024

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide The pleiotropic and protective effects of melatonin have been demonstrated in a variety of animal models of renal injury. While coding RNAs regulated by melatonin in renal tissues are well identified, the functional involvement of long noncoding RNAs (lncRNAs) in melatonin signaling remains undefined. This study identified nuclear enriched abundant transcript 1 ( NEAT 1), a clock-controlled lncRNA that was upregulated by melatonin through the BMAL1/CLOCK heterodimer in renal tubular epithelial cells (TECs). Mechanistic studies showed that melatonin enhanced NEAT 1 expression via increasing BMAL1 stability and thereby the enrichment of BMAL 1 on NEAT 1’s promoter. Further studies have revealed that NEAT 1 promotes the proliferation of TECs by increasing levels of H3K27ac and H3K4me1 at the promoter regions of the proliferation gene MKI 67. Treatment of albumin-injured TECs with melatonin promoted proliferation by transactivating NEAT 1 and restoring the expression levels of core clock genes and MKI 67. Moreover, melatonin treatment ameliorated proteinuria, hypoalbuminemia, and fibrotic lesions, which was correlated with increased levels of core clock genes, H3K27ac, Mki 67, and Neat 1 in experimental MN kidneys. Melatonin mediates a novel regulatory axis, BMAL1- NEAT 1- MKI 67, in TEC proliferation, establishing potential therapeutic targets for MN and other renal diseases.

Source: ACS Pharmacology & Translational Science

DOI: 10.1021/acsptsci.4c00495