Akt2 Affects Periodontal Inflammation via Altering the M1/M2 Ratio

Published on 2020-04-04T12:18:51Z (GMT) by
<div><p>Periodontitis is a bacteria-driven inflammatory destructive disease that leads to attachment loss, bone resorption, and even tooth loss. Accumulating studies revealed that macrophages might play an nonnegligible role during the processes of periodontitis. However, the underlying mechanism remains largely unknown. In this study, we found novel Akt2/JNK1/2/c-Jun and Akt2/miR-155-5p/DET1/c-Jun signaling pathways that regulated the polarization of macrophages and altered periodontal inflammatory status. Through hematoxylin and eosin, immunostaining, and immunofluorescence staining of clinical specimens, a higher number of M1 phenotype macrophage infiltration was found in periodontitis than in normal controls. Flow cytometry and immunofluorescence showed that overexpression of Akt2 in RAW 264.7 cells induced M1 macrophage polarization and decreased M2 polarization, while knockdown of Akt2 exerted an opposite effect. Furthermore, overexpression of Akt2 activated the JNK pathway and then increased the release of proinflammatory mediators, while knockdown of Akt2 downregulated the above genes accordingly. Importantly, the macrophage polarization and the subsequent alteration of pathway molecules induced by overexpression of Akt2 could be rescued by Akt2 and JNK inhibitors. Moreover, JNK inhibition could facilitate M2 polarization of macrophages. In a mouse periodontitis model, the novel signaling pathway as well as clinical phenotype was further verified. Inhibition of Akt2 facilitated macrophage M2 polarization and rescued the bone loss due to periodontitis. Collectively, we identified novel Akt2/JNK1/2/c-Jun and Akt2/miR-155-5p/DET1/c-Jun signaling pathways that regulate macrophage polarization and highlight that Akt2 inhibition promotes M2 polarization of macrophages and can be a novel potential candidate in the treatment of periodontitis.</p></div>

Cite this collection

Wu, X.; Chen, H.; Wang, Y.; Gu, Y. (2020): Akt2 Affects Periodontal Inflammation via Altering the M1/M2 Ratio. SAGE Journals. Collection. https://doi.org/10.25384/SAGE.c.4925814.v1