The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST KLOS) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBME), School & Hospital of Stomatology, Wuhan University, Wuhan, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST KLOS) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBME), School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Biochim Biophys Acta Mol Cell Res. 2021 Mar;1868(3):118923. doi: 10.1016/j.bbamcr.2020.118923. Epub 2020 Dec 5.
The keystone pathogen Porphyromonas gingivalis (P. gingivalis) elicits inflammation and autophagy in periodontal tissues. Transcription factor CXXC-type zinc finger protein 5 (CXXC5) and various signals are sensitive to P. gingivalis invasion. Herein, we investigated the P. gingivalis-elicited autophagy activity, the contribution of CXXC5, and the involvement of signals in cementoblasts, tooth root surface cells crucial in periodontal and periapical regions. After coculture with P. gingivalis, cementoblasts exhibited inflammatory cytokine increase, light chain 3(LC3)-I/II conversion, autophagosome activation, and CXXC5 reduction. Cementoblasts with loss and gain of CXXC5 were developed. CXXC5 silencing suppressed autophagy and inflammation, thereby partially compensating for the effects of P. gingivalis, and vice versa. We then screened potential signals and verified the positive participation of Stat3/Akt/Erk networks through specific inhibitor employment. P. gingivalis and CXXC5 induced autophagy through Beclin1 and Atg5 activation. Intriguingly, Annexin V/PI assay and EdU detection revealed that P. gingivalis promoted apoptosis and repressed cell proliferation. In sum, coculture with P. gingivalis enhanced autophagy activity in cementoblasts, which was partially suppressed by CXXC5 downregulation and mediated by Jak/Stat3, PI3K-Akt, and Erk1/2 signaling. This process probably influenced cell apoptosis and proliferation.
关键病原体牙龈卟啉单胞菌（P. gingivalis）在牙周组织中引发炎症和自噬。转录因子CXXC 型锌指蛋白 5（CXXC5）和各种信号对 P. gingivalis 的入侵敏感。在此，我们研究了 P. gingivalis 诱导的自噬活性、CXXC5 的作用以及在牙周和根尖区域关键的牙骨质细胞中信号的参与。与 P. gingivalis 共培养后，牙骨质细胞表现出炎症细胞因子增加、LC3-I/II 转化、自噬体激活和 CXXC5 减少。开发了缺失和获得 CXXC5 的牙骨质细胞。CXXC5 沉默抑制自噬和炎症，从而部分补偿 P. gingivalis 的作用，反之亦然。然后，我们通过特异性抑制剂的使用筛选了潜在的信号，并验证了 Stat3/Akt/Erk 网络的积极参与。P. gingivalis 和 CXXC5 通过 Beclin1 和 Atg5 的激活诱导自噬。有趣的是，Annexin V/PI 分析和 EdU 检测表明，P. gingivalis 促进细胞凋亡并抑制细胞增殖。总之，与 P. gingivalis 共培养增强了牙骨质细胞中的自噬活性，该活性被 CXXC5 下调部分抑制，并由 Jak/Stat3、PI3K-Akt 和 Erk1/2 信号介导。这个过程可能影响细胞凋亡和增殖。
