title: Periostin controls keratinocyte proliferation and differentiation by interacting with the paracrine IL-1α/IL-6 loop.
abstract: Proliferation and differentiation of keratinocytes are normally well balanced, but this balance can be perturbed in wound healing and is dysregulated in pathological conditions such as atopic dermatitis. Epithelial-mesenchymal interaction affects this event via the cross-talk of cytokines and growth factors. Periostin, a matricellular protein, has an important role during reepithelialization in wound healing and is critical for hyperproliferation of keratinocytes in atopic dermatitis. Here we investigated how periostin regulates proliferation and differentiation of keratinocytes in the epithelial-mesenchymal interactions using a three-dimensional organotypic air-liquid interface coculture system. The release of IL-1α from keratinocytes and subsequent IL-6 production from fibroblasts were critical for keratinocyte proliferation and differentiation. Periostin secreted from fibroblasts was required for IL-1α-induced IL-6 production and enhanced IL-6 production by activation of the NF-κB pathway synergistically with IL-1α. Thus, the combination of an autocrine loop of periostin and a paracrine loop composed of IL-1α and IL-6 regulates keratinocyte proliferation and differentiation in the epithelial-mesenchymal interactions, and periostin tunes the magnitude of keratinocyte proliferation and differentiation by interacting with the paracrine IL-1α/IL-6 loop.
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Masuoka
authors.affiliation: Department of Laboratory Medicine, Saga Medical School, Saga, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiraishi
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Ontsuka
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Inamitsu
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Yamamoto
authors.affiliation: Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Simmons
authors.affiliation: Department of Pathology and Biodefense, Saga Medical School, Saga, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
authors.affiliation: Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.affiliation: Department of Pediatrics, Saga Medical School, Saga, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan; Department of Laboratory Medicine, Saga Medical School, Saga, Japan. Electronic address: kizuhara@cc.saga-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D018920:Coculture Techniques; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009924:Organ Culture Techniques; D019899:Paracrine Communication / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016328:NF-kappa B; C082838:Postn protein, mouse; C577686:interleukin-6, mouse