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Published on: March 24, 2017
Expression of RXFP1 in skin of scleroderma patients and control subjects
N Giordano1, N Volpi, D Franci
1Department 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
Objectives:
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).
Method:
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.
Insights
Reduced expression of the relaxin-2 receptor RXFP1 in systemic sclerosis (SSc) skin may explain why relaxin treatments are ineffective. This study investigated RXFP1 levels in SSc skin cells.
Area of Science:
- Dermatology and cell biology research.
- Investigating molecular mechanisms in fibrotic diseases.
Background:
- Relaxin (RLX) plays a role in extracellular matrix remodeling.
- The circulating isoform RLX-2 is explored for its anti-fibrotic potential in systemic sclerosis (SSc).
- RLX-2 interacts with RXFP1/LGR7 and RXFP2/LGR8 receptors.
Purpose of the Study:
- To determine the expression pattern of the RLX-2 receptor RXFP1 (LGR7) in various human skin cells.
- To compare RXFP1 expression in normal skin versus lesional and unaffected skin from patients with limited SSc (lSSc).
Main Methods:
- Immunolocalization of RXFP1 on skin biopsies and cultured fibroblasts from lSSc patients and controls.
- Western blot analysis of fibroblast lysates to quantify RXFP1 expression.
Main Results:
- RXFP1 exhibited cytoplasmic localization in skin cells of control subjects and non-lesional SSc skin.
- Significantly reduced RXFP1 expression was observed in scleroderma skin.
- Cultured scleroderma fibroblasts showed weak RXFP1 reactivity compared to strong cytoplasmic staining in control fibroblasts.
Conclusions:
- Decreased cellular RXFP1 expression in SSc skin could be a pro-fibrotic factor.
- This reduction may contribute to the limited efficacy of RLX treatments in SSc.
- The underlying cause for decreased RXFP1, potentially linked to high RLX-2 serum levels in SSc, requires further investigation.