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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

miR-29c-3p Accelerates Mucosal Repair in Dextran Sodium Sulfateinduced Ulcerative Colitis Mice through the KDM6B/H3K27me3/LDHA Axis

Author(s): Xia Li*, Chuanming Yin and Jie Li

Volume 30, Issue 6, 2023

Published on: 05 June, 2023

Page: [459 - 468] Pages: 10

DOI: 10.2174/0929866530666230511115213

Price: $65

Abstract

Background: Ulcerative colitis (UC) is an inflammatory intestinal disorder featured by mucosal injury. MicroRNAs (miRNAs) play a role in the pathogenesis underlying UC.

Objectives: This study was conducted to investigate the role of miR-29c-3p in a dextran sodium sulfate (DSS)-induced UC mouse model and provide targets for UC treatment.

Methods: The UC mouse model was established by DSS induction. The expression levels of miR- 29c-3p, lysine-specific demethylase 6B (KDM6B), zonula occludens-1 (ZO-1), Occludin, and lactate dehydrogenase A (LDHA) were detected by real-time quantitative polymerase chain reaction or Western blot assays. The mucosal injury was evaluated by disease activity index (DAI), colon length, Hematoxylin-Eosin staining, and fluorescein isothiocyanate-glucan permeability test. The binding between miR-29c-3p and KDM6B and the occupation of KDM6B or trimethylated H3 lysine 27 (H3K27me3) on the LDHA promoter were analyzed by the dual-luciferase and chromatinimmunoprecipitation assays.

Results: miR-29c-3p was downregulated while KDM6B and LDHA were upregulated in DSS mice. miR-29c-3p overexpression reduced DAI and inflammatory cell infiltration while increasing colon length, intestinal permeability, and levels of ZO-1 and Occludin. miR-29c-3p inhibited KDM6B expression and increased H3K27me3 occupation on the LDHA promoter, thus inhibiting LDHA transcription. Overexpression of KDM6B or LDHA averted the protective role of miR-29c-3p upregulation in mucosal injury.

Conclusion: miR-29c-3p limited KDM6B expression and increased the H3K27me3 occupation on the LDHA promoter to enhance LDHA transcription, moderating mucosal injury and delaying UC progression.

Keywords: Ulcerative colitis, mucosal repair, miR-29c-3p, KDM6B, LDHA, H3K27me3.

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