Open Access

ARTICLE

BET protein inhibitor apabetalone represses Porphyromonas gingivalis LPS-induced macrophage M1 polarization via regulating miR-130a/STAT3 axis

MEIHUA CHEN^1,2, HUIHUI WANG³, XIAOFENG CHEN^1,2, YAN CHEN^1,2, TIANYING BIAN^1,2,*

1 Department of Periodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200001, China
2 Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
3 Department of Stomatology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, China

* Corresponding Author: TIANYING BIAN. Email:

(This article belongs to the Special Issue: Decoding Gene (including circRNA, lincRNA miRNA and mRNA) Expression)

BIOCELL 2022, 46(10), 2281-2289. https://doi.org/10.32604/biocell.2022.020697

Received 07 December 2021; Accepted 16 February 2022; Issue published 13 June 2022

Abstract

Periodontitis is a frequent chronic inflammatory disorder destroying periodontium. Recent studies have revealed the role of bromodomain and extraterminal domain inhibitor (BETi) and microRNA (miR)-130a in regulating macrophage polarization and pro-inflammatory response. However, little is known about whether apabetalone (a novel BETi) and miR-130a are correlated with chronic inflammatory state in periodontitis by regulating macrophage polarization. Here murine RAW264.7 macrophages were applied as an in vitro inflammatory model. After treatment with Porphyromonas gingivalis-derived lipopolysaccharide (Pg LPS) and apabetalone, the expression of macrophage M1 polarization markers and inflammatory cytokines was assessed using real-time PCR, western blot, and enzyme-linked immuno sorbent assay (ELISA). MiR-130a level was assessed using real-time PCR, and the target gene was identified using dual luciferase reporter assay. We demonstrated that apabetalone repressed Pg LPS-induced macrophage M1 polarization in a dose-dependent manner, as evidenced by decreased expression of inducible nitric oxide synthase (iNOS), CD86, and pro-inflammatory cytokines, and increased expression of Arg-1 and CD206. Mechanistically, Pg LPS increased miR-130a expression in macrophages, whereas apabetalone treatment repressed the effect. Functionally, forced expression of miR-130a promoted macrophage M1 polarization, and signal transducer and activator of transcription (STAT)-3 was the direct target gene of miR-130a in the process. Taken together, apabetalone decreases Pg LPS-induced macrophage M1 polarization via regulating miR-130a-3p/STAT3 axis, and may be a promising target for the clinical management of periodontitis.

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