TY  - EJOU
AU  - CHEN, MEIHUA 
AU  - WANG, HUIHUI 
AU  - CHEN, XIAOFENG 
AU  - CHEN, YAN 
AU  - BIAN, TIANYING 

TI  - BET protein inhibitor apabetalone represses <i>Porphyromonas gingivalis</i> LPS-induced macrophage M1 polarization via regulating miR-130a/STAT3 axis
T2  - BIOCELL

PY  - 2022
VL  - 46
IS  - 10
SN  - 1667-5746

AB  - 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 <i>in vitro</i> inflammatory model. After treatment with <i>Porphyromonas gingivalis</i>-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.
KW  - Periodontitis; Macrophage polarization; <i>Porphyromonas gingivalis</i>; BET inhibitor; miRNA

DO  - 10.32604/biocell.2022.020697