PMID- 35472469 OWN - NLM STAT- MEDLINE DCOM- 20220524 LR - 20220809 IS - 1880-3865 (Electronic) IS - 1349-0079 (Print) IS - 1349-0079 (Linking) VI - 64 IP - 2 DP - 2022 Jun TI - Periodontitis promotes the expression of gingival transmembrane serine protease 2 (TMPRSS2), a priming protease for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PG - 229-236 LID - S1349-0079(22)00058-5 [pii] LID - 10.1016/j.job.2022.04.004 [doi] AB - 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. CI - Copyright (c) 2022 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved. FAU - Ohnishi, Tomokazu AU - Ohnishi T AD - Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. FAU - Nakamura, Toshiaki AU - Nakamura T AD - Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. FAU - Shima, Kaori AU - Shima K AD - Department of Oral Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. FAU - Noguchi, Kazuyuki AU - Noguchi K AD - Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. FAU - Chiba, Norika AU - Chiba N AD - Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. FAU - Matsuguchi, Tetsuya AU - Matsuguchi T AD - Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. Electronic address: tmatsugu@dent.kagoshima-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220425 PL - Netherlands TA - J Oral Biosci JT - Journal of oral biosciences JID - 101226721 RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (spike protein, SARS-CoV-2) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (TMPRSS2 protein, human) SB - IM MH - Angiotensin-Converting Enzyme 2 MH - Animals MH - *COVID-19/genetics MH - Gingiva MH - Humans MH - Mice MH - Peptide Hydrolases MH - *Periodontitis MH - SARS-CoV-2 MH - Serine Endopeptidases/genetics MH - Spike Glycoprotein, Coronavirus PMC - PMC9035663 OTO - NOTNLM OT - COVID-19 OT - Gingiva OT - Keratinocytes OT - Periodontitis OT - SARS-CoV-2 EDAT- 2022/04/27 06:00 MHDA- 2022/05/25 06:00 PMCR- 2022/04/25 CRDT- 2022/04/26 20:05 PHST- 2022/03/31 00:00 [received] PHST- 2022/04/15 00:00 [revised] PHST- 2022/04/19 00:00 [accepted] PHST- 2022/04/27 06:00 [pubmed] PHST- 2022/05/25 06:00 [medline] PHST- 2022/04/26 20:05 [entrez] PHST- 2022/04/25 00:00 [pmc-release] AID - S1349-0079(22)00058-5 [pii] AID - 10.1016/j.job.2022.04.004 [doi] PST - ppublish SO - J Oral Biosci. 2022 Jun;64(2):229-236. doi: 10.1016/j.job.2022.04.004. Epub 2022 Apr 25.