title: Distinct expression of adhesion molecules on skin fibroblasts from patients with diffuse and limited systemic sclerosis. A pilot study.
abstract: OBJECTIVE
  . Systemic sclerosis (SSc) is characterized by excessive production of collagen and other components of the extracellular matrix (ECM) by fibroblasts. The ECM receptors, integrins and CD44 (hyaluronan receptor), play a key role in the homeostasis of connective tissue and may also have a role in the pathogenesis of fibrosis. We investigated the expression of integrins and CD44 on skin fibroblasts from patients with limited and diffuse SSc.
  
  
  METHODS
  We studied 13 patients with SSc, 8 with limited SSc, and 5 with diffuse SSc, and 8 control subjects. Fibroblasts were isolated and cultured from biopsies taken from the lesional skin of the second finger of the left hand. Cell-surface expression of beta1, beta3, alpha1-alpha6, alphav integrins, and CD44 was evaluated by immunofluorescence and flow cytometry analysis.
  
  
  RESULTS
  Fibroblasts from limited SSc showed significantly decreased expression of alpha2, alpha3, alpha4 integrins, while diffuse SSc fibroblasts had significantly reduced expression of alpha5, alphav integrins, and CD44. Diffuse SSc also had significantly increased expression of alpha6 integrin on fibroblasts. In controls, the expression of alpha4 and alpha5 correlated positively, while in limited and diffuse SSc it did not.
  
  
  CONCLUSIONS
  This is the first study evaluating separately the expression of adhesion molecules on skin fibroblasts from limited and diffuse subsets of SSc. We detected a distinct pattern of expression with decrease of collagen and fibronectin receptors in limited SSc, and downregulation of fibronectin and hyaluronan receptors in diffuse SSc. These results suggest that changes of fibroblasts/ECM interactions and mechanisms underlying the pathogenesis of fibrosis in SSc may differ in the single subset of the disease.
authors.affiliation: Rheumatology Unit-DIMIMP, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Florenzo
authors.initials: F
authors.lastname: Iannone
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: Paola Chiara Francesca
authors.initials: PC
authors.lastname: Falappone
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Marina
authors.initials: M
authors.lastname: Cinelli
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lapadula
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D010865:Pilot Projects; D038981:Receptors, Collagen / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism; D045743:Scleroderma, Diffuse / Q000378:metabolism* / Q000473:pathology; D045745:Scleroderma, Limited / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000473:pathology
chemical_list: D018960:Hyaluronan Receptors; D016023:Integrins; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin