國家衛生研究院 NHRI:Item 3990099045/16251

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/16251

Title:	Melatonin alleviates albumin-induced tubular cell injury by activating clock-controlled nuclear enriched abundant transcript 1-mediated proliferation
Authors:	Huang, YS;Lu, KC;Chang, YT;Ka, SM;Guo, CY;Hsieh, HY;Shih, HM;Sytwu, HK;Wu, CC
Contributors:	National Institute of Infectious Diseases and Vaccinology
Abstract:	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 (NEAT1), 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 NEAT1 expression via increasing BMAL1 stability and thereby the enrichment of BMAL1 on NEAT1’s promoter. Further studies have revealed that NEAT1 promotes the proliferation of TECs by increasing levels of H3K27ac and H3K4me1 at the promoter regions of the proliferation gene MKI67. Treatment of albumin-injured TECs with melatonin promoted proliferation by transactivating NEAT1 and restoring the expression levels of core clock genes and MKI67. Moreover, melatonin treatment ameliorated proteinuria, hypoalbuminemia, and fibrotic lesions, which was correlated with increased levels of core clock genes, H3K27ac, Mki67, and Neat1 in experimental MN kidneys. Melatonin mediates a novel regulatory axis, BMAL1-NEAT1-MKI67, in TEC proliferation, establishing potential therapeutic targets for MN and other renal diseases.
Date:	2024-10-10
Relation:	ACS Pharmacology and Translational Science. 2024 Oct 10;7(11):3607-3617.
Link to:	http://dx.doi.org/10.1021/acsptsci.4c00495
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2575-9108&DestApp=IC2JCR
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85206443828
Appears in Collections:	[Huey-Kang Sytwu] Periodical Articles

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