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Porphyromonas gingivalis impairs oral epithelial barrier through targeting GRHL2

Item Type:Article
Title:Porphyromonas gingivalis impairs oral epithelial barrier through targeting GRHL2
Creators Name:Chen, W. and Alshaikh, A. and Kim, S. and Kim, J. and Chun, C. and Mehrazarin, S. and Lee, J. and Lux, R. and Kim, R.H. and Shin, K.H. and Park, N.H. and Walentin, K. and Schmidt-Ott, K.M. and Kang, M K
Abstract: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.
Keywords:Oral Mucosa, Periodontal Diseases, Tight Junctions, Lipopolysaccharides, Cell Adhesion, Gene Knockout Techniques, Animals, Mice
Source:Journal of Dental Research
ISSN:0022-0345
Publisher:Sage Publications
Volume:98
Number:10
Page Range:1150-1158
Date:1 September 2019
Official Publication:https://doi.org/10.1177/0022034519865184
PubMed:View item in PubMed

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