Pyroptosis may play a crucial role in modifications of the immune microenvironment in periodontitis

被引:19
作者
Chen, Hang [1 ,2 ,3 ]
Wang, Zhenxiang [1 ,2 ,3 ]
He, Yujuan [4 ]
Peng, Limin [1 ,2 ,3 ]
Zhu, Junlin [1 ,2 ,3 ]
Zhang, Xiaonan [1 ,2 ,3 ]
机构
[1] Chongqing Med Univ, Coll Stomatol, 426 Sunshine Rd, Chongqing, Peoples R China
[2] Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing, Peoples R China
[3] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China
[4] Chongqing Med Univ, Minist Educ, Key Lab Diagnost Med, Dept Lab Med, Chongqing, Peoples R China
基金
中国国家自然科学基金;
关键词
bioinformatics; chronic periodontitis; periodontal immunology; pyroptosis; R PACKAGE; TRANSCRIPTOMES; INFECTIONS; CLEAVAGE;
D O I
10.1111/jre.13035
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Background and objective Published studies proved that both pyroptosis and periodontitis owned a substantial relationship with immunity, and recent research revealed a solid correlation between periodontitis and pyroptosis. While abundant findings have confirmed pyroptosis has a strong impact on the tumor microenvironment, the function of pyroptosis in influencing the periodontitis immune microenvironment remains poorly understood. Thus, we aimed to identify pyroptosis-related genes whose expression signature can well discriminate periodontitis from healthy controls and to comprehend the role of pyroptosis in the periodontitis immune microenvironment. Materials and methods The periodontitis-related datasets were acquired from the Gene Expression Omnibus (GEO) database. A series of bioinformatics analyses were conducted to investigate the underlying mechanism of pyroptosis in the periodontitis immune microenvironment. Infiltrating immunocytes, immunological reaction gene sets, and the human leukocyte antigen (HLA) gene were all investigated as potential linkages between periodontitis immune microenvironment and pyroptosis. Results Twenty-one pyroptosis-related genes were dysregulated. A four-mRNA combined classification model was constructed, and the receiver operating characteristic (ROC) curve analysis demonstrated its prominent classification capabilities. Subsequently, the mRNA levels of the four hub markers (CYCS, CASP3, NOD2, CHMP4B) were validated by quantitative real-time PCR (qRT-PCR). The correlation coefficients between each hub gene and immune characteristics were calculated, and CASP3 exhibited the most significant correlations with the immune characteristics. Furthermore, distinct pyroptosis-related expression patterns were revealed, along with immunological features of each pattern. Afterward, we discovered 1868 pyroptosis phenotype-related genes, 134 of which were related to immunity. According to the functional enrichment analysis, these 134 genes were closely related to cytokine signaling in immune system, and defense response. Finally, a co-expression network was constructed via the 1868 gene expression profiles. Conclusion Four hub mRNAs (CYCS, CASP3, NOD2, and CHMP4B) formed a classification model and concomitant results revealed the crucial role of pyroptosis in the periodontitis immune microenvironment, providing fresh insights into the etiopathogenesis of periodontitis and potential immunotherapy.
引用
收藏
页码:977 / 990
页数:14
相关论文
共 57 条
[1]   Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions [J].
Aglietti, Robin A. ;
Dueber, Erin C. .
TRENDS IN IMMUNOLOGY, 2017, 38 (04) :261-271
[2]   Pyroptosis: host cell death and inflammation [J].
Bergsbaken, Tessa ;
Fink, Susan L. ;
Cookson, Brad T. .
NATURE REVIEWS MICROBIOLOGY, 2009, 7 (02) :99-109
[3]   ImmPort: disseminating data to the public for the future of immunology [J].
Bhattacharya, Sanchita ;
Andorf, Sandra ;
Gomes, Linda ;
Dunn, Patrick ;
Schaefer, Henry ;
Pontius, Joan ;
Berger, Patty ;
Desborough, Vince ;
Smith, Tom ;
Campbell, John ;
Thomson, Elizabeth ;
Monteiro, Ruth ;
Guimaraes, Patricia ;
Walters, Bryan ;
Wiser, Jeff ;
Butte, Atul J. .
IMMUNOLOGIC RESEARCH, 2014, 58 (2-3) :234-239
[4]  
Chapple ILC, 2013, J CLIN PERIODONTOL, V40, pS106, DOI [10.1902/jop.2013.1340011, 10.1111/jcpe.12077]
[5]   Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis [J].
Chen, Qin ;
Liu, Xingguang ;
Wang, Dingyu ;
Zheng, Jisi ;
Chen, Lu ;
Xie, Qianyang ;
Liu, Xiaohan ;
Niu, Sujuan ;
Qu, Guanlin ;
Lan, Jianfeng ;
Li, Jing ;
Yang, Chi ;
Zou, Duohong .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9
[6]   UpSetR: an R package for the visualization of intersecting sets and their properties [J].
Conway, Jake R. ;
Lex, Alexander ;
Gehlenborg, Nils .
BIOINFORMATICS, 2017, 33 (18) :2938-2940
[7]   Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes [J].
Cristescu, Razvan ;
Lee, Jeeyun ;
Nebozhyn, Michael ;
Kim, Kyoung-Mee ;
Ting, Jason C. ;
Wong, Swee Seong ;
Liu, Jiangang ;
Yue, Yong Gang ;
Wang, Jian ;
Yu, Kun ;
Ye, Xiang S. ;
Do, In-Gu ;
Liu, Shawn ;
Gong, Lara ;
Fu, Jake ;
Jin, Jason Gang ;
Choi, Min Gew ;
Sohn, Tae Sung ;
Lee, Joon Ho ;
Bae, Jae Moon ;
Kim, Seung Tae ;
Park, Se Hoon ;
Sohn, Insuk ;
Jung, Sin-Ho ;
Tan, Patrick ;
Chen, Ronghua ;
Hardwick, James ;
Kang, Won Ki ;
Ayers, Mark ;
Dai Hongyue ;
Reinhard, Christoph ;
Loboda, Andrey ;
Kim, Sung ;
Aggarwal, Amit .
NATURE MEDICINE, 2015, 21 (05) :449-U217
[8]   Periodontitis: a polymicrobial disruption of host homeostasis [J].
Darveau, Richard P. .
NATURE REVIEWS MICROBIOLOGY, 2010, 8 (07) :481-490
[9]   Transcriptomes in Healthy and Diseased Gingival Tissues [J].
Demmer, Ryan T. ;
Behle, Jan H. ;
Wolf, Dana L. ;
Handfield, Martin ;
Kebschull, Moritz ;
Celenti, Romanita ;
Pavlidis, Paul ;
Papapanou, Panos N. .
JOURNAL OF PERIODONTOLOGY, 2008, 79 (11) :2112-2124
[10]   The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs [J].
Diepstraten, Sarah T. ;
Anderson, Mary Ann ;
Czabotar, Peter E. ;
Lessene, Guillaume ;
Strasser, Andreas ;
Kelly, Gemma L. .
NATURE REVIEWS CANCER, 2022, 22 (01) :45-64