title: Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is characterized by early endothelial damage evolving to vascular desertification. Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 regulate specific steps in new vessel formation. We undertook this study to determine whether an alteration of the SDF-1/CXCR4 axis might be involved in the pathogenetic mechanisms following ischemic damage during SSc.
  
  
  METHODS
  We enrolled 36 SSc patients and 15 controls. Skin biopsy samples were obtained from each subject, and the expression of SDF-1 and CXCR4 was assessed by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. Furthermore, isolated microvascular endothelial cells (MVECs) from 4 patients with diffuse cutaneous SSc (dcSSc) and 3 controls were analyzed for SDF-1 and CXCR4 by confocal laser scanning microscopy, RT-PCR, and Western blotting.
  
  
  RESULTS
  SDF-1 and CXCR4 were up-regulated in the skin of patients with early (edematous) SSc, both in the diffuse and limited cutaneous forms, and progressively decreased, with the lowest expression in the latest phases of both SSc subsets. MVECs from patients with dcSSc expressed significantly higher amounts of both isoforms of SDF-1 in the early stage of disease, with a progressive reduction of SDF-1 and CXCR4 in later stages. On the surface of cultured MVECs from patients with dcSSc, SDF-1 and CXCR4 colocalized in polarized areas, suggesting that they are activated in vivo and that they are under strict genetic control to retain capping function.
  
  
  CONCLUSIONS
  Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc.
authors.affiliation: University of L'Aquila, L'Aquila, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.forename: Anna
authors.initials: A
authors.lastname: Franca Milia
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Liakouli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pacini
authors.forename: Mirko
authors.initials: M
authors.lastname: Manetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marrelli
authors.forename: Annarita
authors.initials: A
authors.lastname: Toscano
authors.forename: Elisa
authors.initials: E
authors.lastname: Pingiotti
authors.forename: Antonietta
authors.initials: A
authors.lastname: Fulminis
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Roberto
authors.initials: R
authors.lastname: Perricone
authors.forename: Bashar
authors.initials: B
authors.lastname: Kahaleh
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibba-Manneschi
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000473:pathology*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017931:DNA Primers; D019718:Receptors, CXCR4