title: RhoA-JNK Regulates the E-Cadherin Junctions of Human Gingival Epithelial Cells.
abstract: The junctional epithelium (JE) is unique with regard to its wide intercellular spaces and sparsely developed intercellular junctions. Thus, knowledge of the molecular mechanisms that regulate the formation of the intercellular junctions of the junctional epithelium may be essential to understand the pathophysiology of the JE. HOK-16B cells, a normal human gingival epithelial cell line, were used to identify the molecules involved in the regulation of the formation of intercellular E-cadherin junctions between human gingival epithelial cells. Activation of c-Jun N-terminal kinase (JNK) disrupted the intercellular junctions through the dissociation of E-cadherin. The role of JNK in the formation of these E-cadherin junctions was further confirmed by demonstrating that JNK inhibition induced the formation of intercellular E-cadherin junctions. The upstream signaling of JNK was also examined. Activation of the small GTPase RhoA disrupted the formation of E-cadherin junctions between HOK-16B cells, which was accompanied by JNK activation. Disruption of these intercellular junctions upon RhoA activation was prevented when JNK activity was inhibited. In contrast, RhoA inactivation led to HOK-16B cell aggregation and the formation of intercellular junctions, even under conditions in which the cellular junctions were naturally disrupted by growth on a strongly adhesive surface. Furthermore, the JE of mouse molars had high JNK activity associated with low E-cadherin expression, which was reversed in the other gingival epithelia, including the sulcular epithelium. Interestingly, JNK activity was increased in cells grown on a solid surface, where cells showed higher RhoA activity than those grown on soft surfaces. Together, these results indicate that the decreased formation of intercellular E-cadherin junctions within the JE may be coupled to high JNK activity, which is activated by the upregulation of RhoA on solid tooth surfaces.
authors.affiliation: Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, Program of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: G
authors.initials: G
authors.lastname: Lee
authors.affiliation: Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, Program of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, Program of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea hyunmkim@snu.ac.kr.
authors.forename: H-M
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D015820:Cadherins / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D003470:Culture Media; D004789:Enzyme Activation; D004846:Epithelial Attachment / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005353:Fibronectins / Q000737:chemistry; D005881:Gingiva / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000494:pharmacology / Q000502:physiology*
chemical_list: D000873:Anthracenes; D015820:Cadherins; D003470:Culture Media; D005353:Fibronectins; D011500:Protein Synthesis Inhibitors; C432165:pyrazolanthrone; D000841:Anisomycin; D048031:JNK Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein
keywords: cell biology; cell signaling; gingiva; gingivitis; periodontitis; periodontium