Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2024
Historique:
received: 29 09 2023
accepted: 24 02 2024
medline: 18 3 2024
pubmed: 15 3 2024
entrez: 15 3 2024
Statut: epublish

Résumé

Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection. Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2/furin membranous/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal/middle/upper), on a 5-tier scale (0, 1-weak, 1.5 -weak-to-moderate, 2-moderate, 3-strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at p<0.05. All oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively). Oral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-à-vis a comprehensive analysis of the literature.

Sections du résumé

BACKGROUND BACKGROUND
Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection.
METHODS METHODS
Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2/furin membranous/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal/middle/upper), on a 5-tier scale (0, 1-weak, 1.5 -weak-to-moderate, 2-moderate, 3-strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at p<0.05.
RESULTS RESULTS
All oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively).
CONCLUSIONS CONCLUSIONS
Oral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-à-vis a comprehensive analysis of the literature.

Identifiants

pubmed: 38489333
doi: 10.1371/journal.pone.0300269
pii: PONE-D-23-28297
pmc: PMC10942036
doi:

Substances chimiques

Furin EC 3.4.21.75
Angiotensin-Converting Enzyme 2 EC 3.4.17.23

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0300269

Informations de copyright

Copyright: © 2024 Grinstein-Koren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Osnat Grinstein-Koren (O)

Department of Oral Pathology, Oral Medicine and Maxillofacial Imaging, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Michal Lusthaus (M)

Department of Oral Pathology, Oral Medicine and Maxillofacial Imaging, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Hilla Tabibian-Keissar (H)

Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Ilana Kaplan (I)

Department of Oral Pathology, Oral Medicine and Maxillofacial Imaging, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Institute of Pathology, Rabin Medical Center, Petach-Tikva, Israel.

Amos Buchner (A)

Department of Oral Pathology, Oral Medicine and Maxillofacial Imaging, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Ron Ilatov (R)

Goldschleger School of Dental Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Marilena Vered (M)

Department of Oral Pathology, Oral Medicine and Maxillofacial Imaging, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Ayelet Zlotogorski-Hurvitz (A)

Department of Oral Pathology, Oral Medicine and Maxillofacial Imaging, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Department of Oral and Maxillofacial Surgery, Rabin Medical Center, Petach-Tikva, Israel.

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