Inflammation-Associated Senescence Promotes Helicobacter pylori-Induced Atrophic Gastritis.
Inflammation-Associated Senescence Promotes Helicobacter pylori-Induced Atrophic Gastritis.
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炎症相关的衰老促进幽门螺杆菌诱发的萎缩性胃炎
DOI：
10.1016/j.jcmgh.2020.10.015
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发表时间：
2021
影响因子：
7.2
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Cai Q;Shi P;Yuan Y;Peng J;Ou X;Zhou W;Li J;Su T;Lin L;Cai S;He Y;Xu J
细胞衰老与幽门螺杆菌引起的萎缩性胃炎之间的关系尚不清楚。在此，我们探讨细胞衰老在幽门螺杆菌诱导的萎缩性胃炎中的作用及其机制。用幽门螺杆菌感染C57 BL/6 J小鼠用于体内生物学和机制研究。收集患者和小鼠模型的胃癌前病变，并使用衰老相关β-半乳糖苷酶、苏丹黑B和免疫组化染色分析衰老细胞、信号通路和幽门螺杆菌感染。染色质免疫沉淀，荧光素酶报告基因分析，和其他技术被用来探讨潜在的机制在体外。胃粘膜萎缩与细胞衰老密切相关。幽门螺杆菌通过C-X-C基序趋化因子受体2（CXCR 2）信号通路促进胃上皮细胞的衰老。有趣的是，幽门螺杆菌感染不仅上调CXCR 2配体、C-X-C基序趋化因子配体1和8的表达，而且直接通过核因子-κB亚基1转录上调CXCR 2的表达。此外，CXCR 2与p53形成正反馈环，持续促进衰老。在幽门螺杆菌感染的小鼠模型中，药物抑制CXCR 2可减轻粘膜衰老和萎缩，并延迟进一步的癌前病变进展。我们的研究表明，幽门螺杆菌诱导的萎缩性胃炎通过CXCR 2介导的细胞衰老的新机制。抑制CXCR 2信号被认为是一种潜在的针对幽门螺杆菌诱导的萎缩性胃炎的预防性治疗。GEO数据集登录号：GSE 47797和GSE 3556。
The association between cellular senescence and Helicobacter pylori–induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori–induced atrophic gastritis and the underlying mechanism. C57BL/6J mice were infected with H pylori for biological and mechanistic studies in vivo. Gastric precancerous lesions from patients and mouse models were collected and analyzed using senescence-associated beta-galactosidase, Sudan Black B, and immunohistochemical staining to analyze senescent cells, signaling pathways, and H pylori infection. Chromatin immunoprecipitation, luciferase reporter assays, and other techniques were used to explore the underlying mechanism in vitro. Gastric mucosa atrophy was highly associated with cellular senescence. H pylori promoted gastric epithelial cell senescence in vitro and in vivo in a manner that depended on C-X-C motif chemokine receptor 2 (CXCR2) signaling. Interestingly, H pylori infection not only up-regulated the expression of CXCR2 ligands, C-X-C motif chemokine ligands 1 and 8, but also transcriptionally up-regulated the expression of CXCR2 via the nuclear factor-κB subunit 1 directly. In addition, CXCR2 formed a positive feedback loop with p53 to continually enhance senescence. Pharmaceutical inhibition of CXCR2 in an H pylori–infected mouse model attenuated mucosal senescence and atrophy, and delayed further precancerous lesion progression. Our study showed a new mechanism of H pylori–induced atrophic gastritis through CXCR2-mediated cellular senescence. Inhibition of CXCR2 signaling is suggested as a potential preventive therapy for targeting H pylori–induced atrophic gastritis. GEO data set accession numbers: GSE47797 and GSE3556.
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影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
影响因子：
29.4
作者：
Lee, A;ORourke, J;Dixon, MF
通讯作者：
Dixon, MF
DOI：
10.1073/pnas.211053698
发表时间：
2001-10-09
影响因子：
11.1
作者：
Krtolica, A;Parrinello, S;Campisi, J
通讯作者：
Campisi, J
影响因子：
50.3
作者：
Hayakawa Y;Ariyama H;Stancikova J;Sakitani K;Asfaha S;Renz BW;Dubeykovskaya ZA;Shibata W;Wang H;Westphalen CB;Chen X;Takemoto Y;Kim W;Khurana SS;Tailor Y;Nagar K;Tomita H;Hara A;Sepulveda AR;Setlik W;Gershon MD;Saha S;Ding L;Shen Z;Fox JG;Friedman RA;Konieczny SF;Worthley DL;Korinek V;Wang TC
通讯作者：
Wang TC
影响因子：
6.4
作者：
Draper JL;Hansen LM;Bernick DL;Abedrabbo S;Underwood JG;Kong N;Huang BC;Weis AM;Weimer BC;van Vliet AH;Pourmand N;Solnick JV;Karplus K;Ottemann KM
通讯作者：
Ottemann KM