Related Experiment Video
Updated: Aug 18, 2026
Fibroblast-Derived 3D Matrix System Applicable to Endothelial Tube Formation Assay
Published on: December 26, 2019
Impaired growth response to endothelin-1 in scleroderma fibroblasts
Abstract:
Systemic sclerosis (SSc) is characterized by vascular damage and dermal fibrosis. In this study, we examined the endothelin (ET) receptor subtype involved in mitogenic signaling in scleroderma and normal skin fibroblasts. ET-1 stimulated DNA synthesis of normal fibroblasts in serum-deprived cultures. ET-3 had lesser effects on DNA synthesis of normal fibroblasts than ET-1. The growth response to ET-1 in scleroderma fibroblasts was decreased compared to normal fibroblasts. [125I]-ET-1 binding to normal fibroblasts was significantly blocked by excessive amount of unlabeled ET-1 and BQ-123. [125I]-ET-1 binding to scleroderma fibroblasts was significantly decreased compared with normal controls. Immunoblotting analysis showed that the expression of ETA receptor in scleroderma fibroblasts was diminished compared with normal controls. ETA mRNA expression in scleroderma fibroblasts was decreased compared with that of normal fibroblasts. From these results, we conclude that the mitogenic effects of ET in human dermal fibroblasts are mainly mediated through ETA receptors, and that down-regulation of ETA receptors caused the decreased growth response of ET-1 in scleroderma fibroblasts.
Insights
Systemic sclerosis (SSc) involves vascular damage and fibrosis. This study found reduced endothelin ETA receptor expression in SSc fibroblasts, explaining their diminished growth response to endothelin-1.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- Systemic sclerosis (SSc) is a fibrotic disease marked by vascular damage.
- Endothelin (ET) signaling plays a role in fibroblast proliferation.
Purpose of the Study:
- To investigate the endothelin (ET) receptor subtype mediating mitogenic signaling in scleroderma and normal skin fibroblasts.
- To compare ET-1 and ET-3 effects on fibroblast DNA synthesis.
Main Methods:
- Fibroblast cultures from scleroderma and normal skin were used.
- DNA synthesis was measured after ET-1 and ET-3 stimulation.
- Endothelin ETA receptor binding and expression (mRNA and protein) were analyzed.
Main Results:
- ET-1 stimulated DNA synthesis in normal fibroblasts; ET-3 had lesser effects.
- Scleroderma fibroblasts showed a decreased growth response to ET-1 compared to normal fibroblasts.
- Scleroderma fibroblasts exhibited significantly decreased [125I]-ET-1 binding and diminished ETA receptor expression (protein and mRNA) compared to normal controls.
Conclusions:
- Mitogenic effects of ET in human dermal fibroblasts are primarily mediated through ETA receptors.
- Down-regulation of ETA receptors in scleroderma fibroblasts leads to a decreased growth response to ET-1.
More Related Videos
11:38Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
09:10Human Saphenous Vein Endothelial Cell Isolation and Exposure to Controlled Levels of Shear Stress and Stretch
Published on: April 21, 2023
