title: Histamine inhibits differentiation of skin fibroblasts into myofibroblasts.
abstract: Histamine and TGF-β, major mediators secreted by mast cells, are involved in skin inflammation and play critical roles in the pathogenesis of systemic sclerosis. However, the roles of signaling mechanisms in the development of skin fibrosis remain largely unclear. Here we show that histamine suppressed the expression of α smooth muscle actin (αSMA), a marker of myofibroblasts, induced by TGF-β1 in skin fibroblasts. Histamine H1-receptor (H1R), but not H2-receptor (H2R) or H4-receptor (H4R), was expressed on skin fibroblasts at both mRNA and protein levels. Interestingly, an H1R antagonist, but not H2R or H4R antagonists, antagonized the histamine-mediated suppression of αSMA expression by TGF-β1. Correspondingly, phosphorylated Smad2 was detected after treatment with TGF-β1, whereas the addition of histamine inhibited this phosphorylation. Taken together, histamine-H1R decreased TGF-β1-mediated Smad2 phosphorylation and inhibited differentiation of skin fibroblasts into myofibroblasts.
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan; Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang 110022, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Sawamukai
authors.affiliation: Division of Rheumatology, Keio University, Tokyo 160-8582, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan; Pharmacology Research Laboratories I, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakata
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakano
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan. Electronic address: tanaka@med.uoeh-u.ac.jp.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000199:Actins / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology* / Q000276:immunology; D005786:Gene Expression Regulation; D006632:Histamine / Q000276:immunology*; D006801:Humans; D058628:Myofibroblasts / Q000166:cytology* / Q000276:immunology; D010766:Phosphorylation; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000166:cytology* / Q000276:immunology; D051899:Smad2 Protein / Q000737:chemistry / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D011969:Receptors, Histamine H1; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D006632:Histamine
keywords: Histamine; Myofibroblast; Skin fibroblast; Smad; TGF-β1; αSMA