Abstract
Objectives: The oral cavity is one of the main entry sites for SARS-CoV-2. Gingival keratinocytes express transmembrane serine protease 2 (TMPRSS2), responsible for priming the SARS-CoV-2 spike protein. We investigated whether periodontitis increased the expression of TMPRSS2.
Methods: To investigate gene expression in periodontitis, we analyzed the expression of specific genes from (1) the Gene Expression Omnibus (GEO) dataset of 247 human gingival tissues and (2) an experimentally-induced periodontitis mouse model. Human gingival tissues with or without periodontitis were immunohistochemically stained using an anti-TMPRSS2 antibody. Analysis of the TMPRSS2 promoter was performed using a ChIP-Atlas dataset. TMPRSS2 expression was detected in cultured human keratinocytes using quantitative reverse transcription (qRT)-PCR and Western blot analysis.
Results: GEO dataset analysis and an experimentally-induced periodontitis model revealed increased expression of TMPRSS2 in periodontitis gingiva. The keratinocyte cell membrane in periodontitis gingiva was strongly immunohistochemically stained for TMPRSS2. Using ChIP-Atlas and GEO datasets, we screened for transcription factors that bind to the TMPRSS2 promoter region. We found one candidate, estrogen receptor 1 (ESR1), highly expressed in periodontitis gingiva. Analysis of the GEO dataset revealed a correlation between ESR1 and TMPRSS2 expression in gingival tissues. An ESR1 ligand induced TMPRSS2 expression in cultured keratinocytes.
Conclusions: Periodontitis increases TMPRSS2 expression in the cell membrane of gingival keratinocytes.
Keywords: COVID-19; Gingiva; Keratinocytes; Periodontitis; SARS-CoV-2.
【저자키워드】 COVID-19, keratinocytes, SARS-CoV-2., Periodontitis, Gingiva, 【초록키워드】 SARS-CoV-2, TMPRSS2, Gene Expression, antibody, Human, Estrogen, Spike protein, western blot, SARS-CoV-2 spike protein, dataset, reverse transcription, transmembrane serine protease 2, correlation, expression, Quantitative, Periodontitis, Ligand, Analysis, Gingiva, oral cavity, transcription factor, transcription factors, estrogen receptor, Serine, increased expression, tissue, tissues, transmembrane serine protease, TMPRSS2 expression, priming, Gene Expression Omnibus, Express, ESR1, Western blot analysis, datasets, ChIP, promoter, promoter region, cell membrane, GEO dataset, responsible, analyzed, investigated, was performed, screened, increase, expressed, anti-TMPRSS2, GEO, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, coronavirus, protease, expression, acute respiratory syndrome, priming, promote,