endothelin-1 and Nephrogenic-Fibrosing-Dermopathy

endothelin-1 has been researched along with Nephrogenic-Fibrosing-Dermopathy* in 1 studies

Other Studies

1 other study(ies) available for endothelin-1 and Nephrogenic-Fibrosing-Dermopathy

ArticleYear
Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis.
    Experimental dermatology, 2014, Volume: 23, Issue:9

    Nephrogenic systemic fibrosis (NSF) is characterized by systemic fibrosis and abnormal calcification in patients with severe renal dysfunction. It is considered that gadolinium (Gd)-containing contrast agents used for magnetic resonance imaging trigger the development of NSF. However, the causative role of Gd and the mechanism of Gd-induced fibrosis and calcification in NSF are unknown. Recently, it has been known that endothelin-1 (ET-1)/ET receptor (ETR) signalling regulates fibrosis and calcification. The objective was to elucidate the role of ET-1/ETR signalling in Gd-induced fibrosis and calcification in NSF. First, we demonstrated that Gd enhanced proliferation and calcification of human adipose tissue-derived mesenchymal stem cells (hMSC) in vitro. Next, we examined the expression of ET-1 and ETR-A in hMSC using proliferation or calcification assay. ET-1 and ETR-A expression in hMSC treated with Gd were elevated. ET-1/ETR signalling inhibitor, bosentan, inhibited Gd-induced proliferation and calcification of hMSC. In addition, bosentan inhibited Gd-induced phosphorylation of ERK and Akt in hMSC. Plasma ET-1 levels of the patients were significantly higher than these of normal individuals and systemic sclerosis patients. In immunofluorescence staining, the expression of ETR-A in fibroblasts in dermal fibrosis lesion of NSF was increased. We conclude that Gd induces proliferation and calcification of hMSC via enhancement of ET-1/ETR signalling. Our results contribute to understand the pathogenesis of NSF.

    Topics: Adolescent; Bosentan; Calcinosis; Cell Proliferation; Cells, Cultured; Contrast Media; Endothelin Receptor Antagonists; Endothelin-1; Gadolinium; Humans; Magnetic Resonance Imaging; Male; Mesenchymal Stem Cells; Middle Aged; Nephrogenic Fibrosing Dermopathy; Receptor, Endothelin A; Signal Transduction; Sulfonamides

2014