title: The discovery of epidermal tight junctions.
abstract: It was previously thought that the skin barrier is composed singly by the stratum corneum. However, this concept was overturned by the report of Tsukita's group in 2002. They convinced us that tight junctions exist in the stratum granulosum of the epidermis, with the constituent proteins being occludin, claudin-1 and claudin-4. However, more than 30 years before this, Hashimoto et al. described the possible existence of tight junctions in the epidermis in 'Intercellular spaces of the human epidermis as demonstrated with lanthanum' in 1971. Dr. Hashimoto observed lanthanum nitrate-injected human skin by electron microscopy. He discovered that the injected lanthanum penetrated the intercellular spaces of the basal and spinous layers of the epidermis and then moved towards the skin surface until penetration was halted in the granular cell layer near the stratum corneum. He described the cell-to-cell adhesion structures that blocked the movement of lanthanum as 'truly tight junctions'. Thus, this was the first description of the existence of tight junctions in the epidermis. However, the presence of these structures was denied by others and was forgotten. Thanks to the discovery of claudin, the existence of tight junctions between epidermal keratinocytes was finally confirmed. It is interesting that Hashimoto's finding was eventually proved to be correct three decades later as a result of progress in molecular biology. This article encourages us to recognize the importance of careful observation in the molecular biology era.
authors.affiliation: Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ozawa
authors.forename: Koji
authors.initials: K
authors.lastname: Sugawara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuruta
mesh_terms: D002462:Cell Membrane; D005110:Extracellular Space / Q000166:cytology*; D006801:Humans; D007811:Lanthanum; D008297:Male; D012867:Skin / Q000166:cytology*; D013194:Staining and Labeling
chemical_list: D007811:Lanthanum
keywords: electron microscopy; keratinocyte; tight junction