Akt2 Affects Periodontal Inflammation via Altering the M1/M2 Ratio
Akt2 Affects Periodontal Inflammation via Altering the M1/M2 Ratio
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Akt2 通过改变 M1/M2 比率影响牙周炎症
DOI：
10.1177/0022034520910127
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发表时间：
2020-03
影响因子：
7.6
通讯作者：
Gu Y.
中科院分区：
文献类型：
--
作者：
Wu X.;Chen H.;Wang Y.;Gu Y.
牙周炎是一种细菌驱动的炎症性破坏性疾病，可导致附着丧失、骨吸收，甚至牙齿脱落。越来越多的研究表明，巨噬细胞在牙周炎的发病过程中可能起着不可忽视的作用。然而，其基本机制在很大程度上仍然未知。在这项研究中，我们发现了新的Akt 2/JNK 1/2/c-Jun和Akt 2/miR-155- 5 p/DET 1/c-Jun信号通路，它们调节巨噬细胞的极化并改变牙周炎性状态。通过苏木精-伊红染色、免疫组化染色和免疫荧光染色，发现牙周炎组中M1表型巨噬细胞浸润的数量高于正常对照组。流式细胞术和免疫荧光显示，Akt 2在RAW 264.7细胞中的过表达诱导M1巨噬细胞极化并降低M2极化，而敲低Akt 2则产生相反的效果。此外，过表达Akt 2激活JNK通路，然后增加促炎介质的释放，而敲低Akt 2相应地下调上述基因。重要的是，Akt 2和JNK抑制剂可以挽救由Akt 2过表达诱导的巨噬细胞极化和随后的通路分子改变。此外，JNK抑制可促进巨噬细胞的M2极化。在小鼠牙周炎模型中，新的信号通路以及临床表型得到进一步验证。抑制Akt 2促进巨噬细胞M2极化并挽救因牙周炎引起的骨丢失。总的来说，我们鉴定了调节巨噬细胞极化的新型Akt 2/JNK 1/2/c-Jun和Akt 2/miR-155- 5 p/DET 1/c-Jun信号通路，并强调Akt 2抑制促进巨噬细胞的M2极化，可以成为治疗牙周炎的新型潜在候选者。
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.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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