title: Khat alters the phenotype of in vitro-reconstructed human oral mucosa.
abstract: Khat-chewing has been associated with oral lesions including oral cancer, but the mechanisms leading to their development are not known. We hypothesized that khat interferes with the physiological processes of the oral mucosa, such as cell proliferation and differentiation, and aimed at investigating the effects of khat exposure on in vitro-reconstructed human normal buccal mucosa. Khat decreased cell proliferation, epithelial thickness, and cytokeratin 13 expression, while inducing premature expression of p21(Waf1/Cip1), transglutaminases, involucrin, and filaggrin. This suggests that khat is able to induce abnormal differentiation of the buccal epithelium. Khat-induced alterations were accompanied by increased levels of p38 and were reversed by p38 inhibition, pointing to p38 as the key player in this process. The morphological changes described herein mirror the in vivo changes previously described in khat users, and demonstrate for the first time that khat induces pathological alterations in human buccal mucosa, providing evidence that raises concerns about the effects of khat use on oral health.
authors.affiliation: Section for Pathology, The Gade Institute, University of Bergen, Norway.
authors.forename: O M
authors.initials: OM
authors.lastname: Lukandu
authors.forename: E
authors.initials: E
authors.lastname: Neppelberg
authors.forename: O K
authors.initials: OK
authors.lastname: Vintermyr
authors.forename: A C
authors.initials: AC
authors.lastname: Johannessen
authors.forename: D E
authors.initials: DE
authors.lastname: Costea
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D029754:Catha / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D000091344:Filaggrin Proteins; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D012016:Reference Values; D018709:Statistics, Nonparametric
chemical_list: D018797:Cell Cycle Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins