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. Conclusion. Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc.

Cipriani, P., Milia, A., Liakouli, V., Pacini, A., Manetti, M., Marrelli, A., et al. (2006). Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications. ARTHRITIS AND RHEUMATISM, 54(9), 3022-3033 [10.1002/art.22047].

Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications

PERRICONE, ROBERTO;
2006-01-01

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. Conclusion. Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc.
2006
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - MEDICINA INTERNA
English
chemokine receptor CXCR4; stromal cell derived factor 1; adult; angiogenesis; article; blood vessel; clinical article; confocal laser microscopy; controlled study; diffuse scleroderma; drug targeting; endothelium cell; female; genetic regulation; human; human cell; human tissue; immunohistochemistry; male; microvasculature; nucleotide sequence; pathogenicity; priority journal; protein expression; protein function; protein localization; reverse transcription polymerase chain reaction; skin biopsy; skin cell; systemic sclerosis; Western blotting; Adult; Aged; Biopsy; Chemokines, CXC; DNA Primers; Endothelium, Vascular; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Male; Middle Aged; Receptors, CXCR4; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Scleroderma, Systemic; Skin
Cipriani, P., Milia, A., Liakouli, V., Pacini, A., Manetti, M., Marrelli, A., et al. (2006). Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications. ARTHRITIS AND RHEUMATISM, 54(9), 3022-3033 [10.1002/art.22047].
Cipriani, P; Milia, A; Liakouli, V; Pacini, A; Manetti, M; Marrelli, A; Toscano, A; Pingiotti, E; Fulminis, A; Guiducci, S; Perricone, R; Kahaleh, B; Matucci Cerinic, M; Ibba Manneschi, L; Giacomelli, R
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

Questo articolo è pubblicato sotto una Licenza Licenza Creative Commons Creative Commons

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/43307
Citazioni
  • ???jsp.display-item.citation.pmc??? 24
  • Scopus 61
  • ???jsp.display-item.citation.isi??? 57
social impact