title: Expressions of isopeptide bonds and corneodesmosin in middle ear cholesteatoma.
abstract: OBJECTIVE
  Isopeptide bonds form cross-links between constituent proteins in the horny layer of the epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes, which bind corneocytes together. Both play important roles in maintaining epidermal barrier functions. In the present study, we investigated the expressions of isopeptide bonds, CDSN, and related enzymes in middle ear cholesteatoma in comparison with the skin.
  
  
  METHODS
  Prospective case series of patients with middle ear cholesteatoma.
  
  
  METHODS
  Tertiary medical institute.
  
  
  METHODS
  Cholesteatoma and normal postauricular skin were collected from patients with acquired middle ear cholesteatoma during tympanomastoidectomy.
  
  
  METHODS
  Expression of e-(g-glutamyl)lysine isopeptide bonds was examined by immunohistochemistry; Expressions of transglutaminase (TGase)1, TGase2, TGase3, and TGase5 by immunohistochemistry and quantitative RT-PCR (qRT-PCR); expression of CDSN by immunohistochemistry, qRT-PCR, and Western blot; and expressions of tissue kallikrein-related peptidase (KLK)5, KLK7, KLK14, and serine peptidase inhibitor Kazal type 5 (SPINK5) by qRT-PCR.
  
  
  RESULTS
  TGase2 was higher (P=0.0046) and TGase5 was lower (P=0.0008) in cholesteatoma than in the postauricular skin. Immunoreactivity for isopeptide bonds was localized in the granular and horny layers, and was not different between the two tissues. Immunoreactivity for CDSN was localized in the granular layer, and was lower in cholesteatoma than in the skin (P=0.0090). Western blot and qRT-PCR confirmed that the expression of CDSN was lower in cholesteatoma than in the skin. Expressions of KLK5, KLK7, KLK14, or SPINK5 were not different between the two tissues.
  
  
  CONCLUSIONS
  These results indicate that the production of CDSN is likely to be suppressed in cholesteatoma, which would account, at least in part, for the mechanical fragility and increased permeability of the cholesteatoma epithelium.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koizumi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kawaguchi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: J-I
authors.initials: JI
authors.lastname: Ohkubo
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ikezaki
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hohchi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashida
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D000074163:Serine Peptidase Inhibitor Kazal-Type 5 / Q000378:metabolism; D020840:Tissue Kallikreins / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D015415:Biomarkers; C109656:CDSN protein, human; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D011503:Transglutaminases; D020840:Tissue Kallikreins