title: Expression of RXFP1 in skin of scleroderma patients and control subjects.
abstract: OBJECTIVE
  Relaxin (RLX) is involved in extracellular matrix and collagen remodelling. The therapeutic role of the circulating isoform RLX-2 as an anti-fibrotic factor in systemic sclerosis (SSc) has been investigated. Several RLX family peptide receptors (RXFPs) are recognized in humans: RLX-2 is a ligand for RXFP1/LGR7 and RXFP2/LGR8. The aim of this study was to define the pattern of expression of LGR7 in different types of human skin cells and to compare normal skin with lesional and unaffected skin from patients with limited SSc (lSSc).
  
  
  METHODS
  We analysed RXFP1 immunolocalization on skin biopsies and cultured fibroblasts from lSSc patients and control subjects. Western blot analysis was carried out on fibroblast lysates.
  
  
  RESULTS
  RXFP1 showed cytoplasmic localization on skin cells from control subjects and non-lesional skin from lSSc patients: keratinocytes, gland epithelial cells, endothelium, smooth muscle cells, and fibroblasts. Immunogold electron microscopy confirmed a diffuse epithelial cytoplasmic localization of RXFP1. A substantially lower RXFP1 expression was observed in scleroderma skin, with a lack of staining in most cells. Occasional weak reactivity was observed in cultured scleroderma fibroblasts, while control fibroblasts showed a diffuse cytoplasmic immunoreactivity of RXFP1, confirmed by Western blot analysis.
  
  
  CONCLUSIONS
  The decreased cellular expression of RLX-2 receptor RXFP1 in scleroderma skin might represent a pro-fibrotic factor and contribute to the substantial inefficacy of RLX treatment in SSc, as reported in the literature. The pathophysiology of the decrease in RXFP1 may be linked to high RLX-2 serum levels previously detected in SSc, but it has yet to be elucidated.
authors.affiliation: Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena University Hospital Santa Maria alle Scotte, Viale Bracci, Siena, Italy. giordanon@unisi.it
authors.forename: N
authors.initials: N
authors.lastname: Giordano
authors.forename: N
authors.initials: N
authors.lastname: Volpi
authors.forename: D
authors.initials: D
authors.lastname: Franci
authors.forename: C
authors.initials: C
authors.lastname: Corallo
authors.forename: A
authors.initials: A
authors.lastname: Fioravanti
authors.forename: P
authors.initials: P
authors.lastname: Papakostas
authors.forename: A
authors.initials: A
authors.lastname: Montella
authors.forename: M
authors.initials: M
authors.lastname: Biagioli
authors.forename: M
authors.initials: M
authors.lastname: Fimiani
authors.forename: G
authors.initials: G
authors.lastname: Grasso
authors.forename: M M
authors.initials: MM
authors.lastname: Muscettola
authors.forename: R
authors.initials: R
authors.lastname: Guerranti
authors.forename: D
authors.initials: D
authors.lastname: Vannoni
authors.forename: M
authors.initials: M
authors.lastname: Galeazzi
authors.forename: R
authors.initials: R
authors.lastname: Nuti
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000473:pathology
chemical_list: C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide