title: Possible involvement of epithelial-mesenchymal transition in fibrosis associated with IgG4-related Mikulicz's disease.
abstract: OBJECTIVE
  Immunoglobulin G4 (IgG4)-related Mikulicz's disease (MD) is a fibrosis-associated inflammatory disease, often accompanied by lacrimal gland swelling. Although much attention has been paid to the inflammatory aspects of this disease, the mechanisms of the fibrotic processes are still unclear. We focused on the fibrotic changes occurring in the lacrimal glands of IgG4-related MD patients, by examining molecules involved in the epithelial-mesenchymal transition (EMT).
  
  
  METHODS
  Lacrimal gland tissue specimens were obtained from 3 IgG4-related MD patients and 3 control patients with Sjögren's syndrome (SS). The glands were examined by immunohistochemistry and transmission electron microscopy.
  
  
  RESULTS
  Storiform fibrosis, a characteristic of IgG4-related MD, was observed in the lacrimal glands of IgG4-related MD, but rarely in those of SS. Reduced E-cadherin expression, increased phalloidin-stained filamentous actin, and increased α-smooth muscle actin, snail, and heat-shock protein 47 levels were observed in the lacrimal glands of IgG4-related MD compared with those of SS. Transmission electron microscopy revealed an abnormal periodicity of collagen bundles, and basal membrane thickening in the IgG4-related MD compared with that in the SS tissues.
  
  
  CONCLUSIONS
  EMT-like changes were frequently observed in the lacrimal gland epithelia from patients with IgG4-related MD. Thus, EMT may be involved in the pathology of IgG4-related MD fibrosis.
authors.affiliation: a Department of Ophthalmology , Keio University School of Medicine , Tokyo , Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukui
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Shigeto
authors.initials: S
authors.lastname: Shimmura
authors.forename: Shin
authors.initials: S
authors.lastname: Hatou
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ichihashi
authors.forename: Saori
authors.initials: S
authors.lastname: Yaguchi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hirayama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawakita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000328:Adult; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008882:Mikulicz' Disease / Q000150:complications / Q000276:immunology* / Q000473:pathology; D012469:Salivary Glands / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000150:complications* / Q000276:immunology / Q000473:pathology
chemical_list: D007074:Immunoglobulin G
keywords: Epithelial–mesenchymal transition; Fibrosis; IgG4-related disease; Lacrimal gland; Mikulicz's disease