Open Access
ARTICLE
BET protein inhibitor apabetalone represses Porphyromonas gingivalis LPS-induced macrophage M1 polarization via regulating miR-130a/STAT3 axis
MEIHUA CHEN1,2, HUIHUI WANG3, XIAOFENG CHEN1,2, YAN CHEN1,2, TIANYING BIAN1,2,*
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.
Keywords
Cite This Article
CHEN, M., WANG, H., CHEN, X., CHEN, Y., BIAN, T. (2022). BET protein inhibitor apabetalone represses
Porphyromonas gingivalis LPS-induced macrophage M1 polarization via regulating miR-130a/STAT3 axis.
BIOCELL, 46(10), 2281–2289. https://doi.org/10.32604/biocell.2022.020697