title: Tight junction protein claudin-4 is modulated via ΔNp63 in human keratinocytes.
abstract: In the epidermis, tight junction (TJ) structure is specifically located in the stratum granulosum, where the expression of ΔNp63, a p53 family transcription factor, is attenuated. Since the relationship between ΔNp63 and barrier function has not been fully uncovered, we assessed expression profiles of TJ proteins in skin tissues and cultured keratinocytes. The results showed that expression of ΔNp63 and that of claudin-4 were inversely correlated in healthy human epidermis. In vitro studies using HaCaT keratinocytes revealed functional relevance of ΔNp63 and claudin-4. Curiously, Toll-like receptor (TLR)-3 ligand, which is known to be liberated from damaged cells, suppressed ΔNp63 expression and concomitantly upregulated claudin-4 expression in primary keratinocytes. More interestingly, a broad expression pattern of claudin-4 was found in the epidermis of atopic dermatitis (AD), a barrier defect disorder, which contains ΔNp63-lacking keratinocytes as we reported previously. Therefore, upregulation of claudin-4 expression regulated by ΔNp63 might be associated with complementary or repair responses of damaged keratinocytes with AD.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. Electronic address: kuboteru@sapmed.ac.jp.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. Electronic address: k.sugimoto@victorchang.edu.au.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
mesh_terms: D001706:Biopsy; D002454:Cell Differentiation; D062506:Claudin-4 / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4; D008024:Ligands; D034741:RNA, Small Interfering; C495344:TLR3 protein, human; C115051:TP63 protein, human; D051196:Toll-Like Receptor 3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Claudin-4; Keratinocyte; Tight junction; ΔNp63