High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

The oral mucosa is a site of intense immune activity, where a large variety of immune cells meet to provide a first line of defense against pathogenic organisms. Interestingly, the oral mucosa is exposed to a plethora of antigens from food and commensal bacteria that must be tolerated. The mechanisms that enable this tolerance are not yet fully defined. Many works have focused on active immune mechanisms involving dendritic and regulatory T cells. However, epithelial cells also make a major contribution to tolerance by influencing both innate and adaptive immunity. Therefore, the tolerogenic mechanisms concurring in the oral mucosa are intertwined. Here, we review them systematically, paying special attention to the role of oral epithelial cells.

Download Full-text

Association between Mobile Phone Using and DNA Damage of Epithelial Cells of the Oral Mucosa

Journal of Biotechnology and Biomedicine ◽

10.26502/jbb.2642-91280027 ◽

2020 ◽

Vol 03 (02) ◽

Author(s):

Ahmad M Khalil ◽

Israa F Alemam ◽

Khaled M Al-Qaoud

Keyword(s):

Dna Damage ◽

Epithelial Cells ◽

Mobile Phone ◽

Oral Mucosa

Download Full-text

Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry

10.1101/2020.04.18.047951 ◽

2020 ◽

Cited By ~ 9

Author(s):

Mei Zhong ◽

Bing-peng Lin ◽

Hong-bin Gao ◽

Andrew J Young ◽

Xin-hong Wang ◽

...

Keyword(s):

Epithelial Cells ◽

Oral Mucosa ◽

Cardiac Tissue ◽

Clinical Care ◽

Host Cells ◽

Mucosal Tissues ◽

Mucosal Cells ◽

Key Factor ◽

Significant Expression ◽

Epithelial Layers

AbstractBackgroundLeading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited.MethodsIn order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level.ResultsThe bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results.ConclusionsBased on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.

Download Full-text

Porphyromonas gingivalis Impairs Oral Epithelial Barrier through Targeting GRHL2

Journal of Dental Research ◽

10.1177/0022034519865184 ◽

2019 ◽

Vol 98 (10) ◽

pp. 1150-1158 ◽

Cited By ~ 5

Author(s):

W. Chen ◽

A. Alshaikh ◽

S. Kim ◽

J. Kim ◽

C. Chun ◽

...

Keyword(s):

Epithelial Cells ◽

Oral Mucosa ◽

Porphyromonas Gingivalis ◽

Oral Bacteria ◽

Conditional Knockout ◽

Epithelial Barrier ◽

Wild Type ◽

Oral Epithelial ◽

Junction Proteins

Oral mucosa provides the first line of defense against a diverse array of environmental and microbial irritants by forming the barrier of epithelial cells interconnected by multiprotein tight junctions (TJ), adherens junctions, desmosomes, and gap junction complexes. Grainyhead-like 2 (GRHL2), an epithelial-specific transcription factor, may play a role in the formation of the mucosal epithelial barrier, as it regulates the expression of the junction proteins. The current study investigated the role of GRHL2 in the Porphyromonas gingivalis ( Pg)–induced impairment of epithelial barrier functions. Exposure of human oral keratinocytes (HOK-16B and OKF6 cells) to Pg or Pg-derived lipopolysaccharides ( Pg LPSs) led to rapid loss of endogenous GRHL2 and the junction proteins (e.g., zonula occludens, E-cadherin, claudins, and occludin). GRHL2 directly regulated the expression levels of the junction proteins and the epithelial permeability for small molecules (e.g., dextrans and Pg bacteria). To explore the functional role of GRHL2 in oral mucosal barrier, we used a Grhl2 conditional knockout (KO) mouse model, which allows for epithelial tissue-specific Grhl2 KO in an inducible manner. Grhl2 KO impaired the expression of the junction proteins at the junctional epithelium and increased the alveolar bone loss in the ligature-induced periodontitis model. Fluorescence in situ hybridization revealed increased epithelial penetration of oral bacteria in Grhl2 KO mice compared with the wild-type mice. Also, blood loadings of oral bacteria (e.g., Bacteroides, Bacillus, Firmicutes, β- proteobacteria, and Spirochetes) were significantly elevated in Grhl2 KO mice compared to the wild-type littermates. These data indicate that Pg bacteria may enhance paracellular penetration through oral mucosa in part by targeting the expression of GRHL2 in the oral epithelial cells, which then impairs the epithelial barrier by inhibition of junction protein expression, resulting in increased alveolar tissue destruction and systemic bacteremia.

Download Full-text

Production and characterization of an in vitro engineered human oral mucosa

Biochemistry and Cell Biology ◽

10.1139/o01-237 ◽

2002 ◽

Vol 80 (2) ◽

pp. 189-195 ◽

Cited By ~ 38

Author(s):

Mahmoud Rouabhia ◽

Noëlla Deslauriers

Keyword(s):

Tissue Engineering ◽

Epithelial Cells ◽

Oral Mucosa ◽

Oral Diseases ◽

Ki 67 ◽

Necrosis Factor Alpha ◽

Engineering Technology ◽

Cell Monolayers ◽

Factor Alpha

The role of epithelial cells in oral pathologies is poorly understood. Until now, most studies have used normal or transformed epithelial cell monolayers, a system that largely bypasses oral mucosal complexity. To overcome these limitations, an engineered human oral mucosa (EHOM) model has been produced and characterized. Following histological and immunohistochemical analyses, EHOM showed well-organized and stratified tissues in which epithelial cells expressed proliferating keratins such as Ki-67, K14, and K19 and also differentiating keratin (K10). In this model, epithelial cells interacted with fibroblasts in the lamina propria by secreting basement membrane proteins (laminins) and by expressing integrins (β1 and α2β1). Cytokine analyses using cultured supernatants showed that cells in EHOM were able to secrete interleukins (IL) including IL-1β and IL-8 and tumor necrosis factor alpha (TNF-α). Finally, cells in this engineered model were able to secrete different metalloproteinases such as gelatinase-A and gelatinase-B. In conclusion, using tissue engineering technology, we produced well-organized EHOM tissues. It is anticipated that this model will be useful for examining mechanisms involved in oral diseases under controlled conditions by modeling the interactions between mucosa and microorganisms in the oral cavity.Key words: tissue engineering, oral mucosa, periodontitis, keratinocytes, fibroblasts.

Download Full-text