title: Differential expression of junctional adhesion molecules in different stages of systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is characterized by early perivascular inflammation, microvascular endothelial cell (MVEC) activation/damage, and defective angiogenesis. Junctional adhesion molecules (JAMs) regulate leukocyte recruitment to sites of inflammation and ischemia-reperfusion injury, vascular permeability, and angiogenesis. This study was undertaken to investigate the possible role of JAMs in SSc pathogenesis.
  
  
  METHODS
  JAM-A and JAM-C expression levels in skin biopsy samples from 25 SSc patients and 15 healthy subjects were investigated by immunohistochemistry and Western blotting. Subcellular localization of JAMs in cultured healthy dermal MVECs and SSc MVECs was assessed by confocal microscopy. Serum levels of soluble JAM-A (sJAM-A) and sJAM-C in 64 SSc patients and 32 healthy subjects were examined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In control skin, constitutive JAM-A expression was observed in MVECs and fibroblasts. In early-stage SSc skin, JAM-A expression was strongly increased in MVECs, fibroblasts, and perivascular inflammatory cells. In late-stage SSc, JAM-A expression was decreased compared with controls. JAM-C was weakly expressed in control and late-stage SSc skin, while it was strongly expressed in MVECs, fibroblasts, and inflammatory cells in early-stage SSc. Surface expression of JAM-A was higher in early-stage SSc MVECs and increased in healthy MVECs stimulated with early-stage SSc sera. JAM-C was cytoplasmic in resting healthy MVECs, while it was recruited to the cell surface upon challenge with early-stage SSc sera. Early-stage SSc MVECs exhibited constitutive surface JAM-C expression. In SSc, increased levels of sJAM-A and sJAM-C correlated with early disease and measures of vascular damage.
  
  
  CONCLUSIONS
  Our findings indicate that JAMs may participate in MVEC activation, inflammatory processes, and impaired angiogenesis in different stages of SSc.
authors.affiliation: Azienda Ospedaliero-Universitaria Careggi (AOUC), Excellence Centre for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOthe), Department of Anatomy, Histology, and Forensic Medicine, University of Florence, Florence, Italy. mirkomanetti@yahoo.it
authors.forename: Mirko
authors.initials: M
authors.lastname: Manetti
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Eloisa
authors.initials: E
authors.lastname: Romano
authors.forename: Irene
authors.initials: I
authors.lastname: Rosa
authors.forename: Claudia
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mello
authors.forename: Anna Franca
authors.initials: AF
authors.lastname: Milia
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Conforti
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibba-Manneschi
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
mesh_terms: D015153:Blotting, Western; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D062726:Junctional Adhesion Molecules / Q000097:blood / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome
chemical_list: D062726:Junctional Adhesion Molecules