Vascular endothelial cells and mesenchymal myofibroblasts play a central role in the pathogenesis of systemic sclerosis (SSc). Remodeling processes of the connective tissue leading to excessive production of collagen and microvasular injuries result in fibrosis of skin and other organs. Activated mesenchymal myofibroblasts mostly contribute to a fibrotic state. Interestingly, vascular endothelial cells can differentiate to myofibroblast-like cells via endothelial to mesenchymal transition (EMT). Previously, we reported that the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) has a protective potential and is the mediator of its effects in human dermal fibroblasts and experimentally induced skin fibrosis. Here, we started to explore a potential novel facet of cutaneous fibrosis research by analysing the impact of alpha7nAChR on EMT in human dermal microvascular endothelial cells (HDMEC). Our first data revealed expression of the alpha7nAChR in primary HDMEC at RNA level using semi-quantitative RT-PCR. We also confirmed the presence of this receptor in the cell line HMEC-1, an experimental tool for EMT research due to a high expression of the endothelial cell marker CD31 as shown by FACS analysis. At protein level we also demonstrate robust expression of this receptor via Western immunoblotting in HDMEC. Immunofluorescence analysis with specific anti-alpha7nAChR antibodies confirmed expression and a cell membrane associated localisation of this receptor in HDMEC. Finally, we demonstrated the functionality of the alpha7nAChR in HDMEC by measurements of calcium influx using alpha7nAChR agonists and the antagonist alpha-bungarotoxin. Future work will disclose whether this receptor is also functional in the cell line HMEC-1. Intensified future research on the dermal endothelial cell system is currently being conducted to precisely dissect the role of the alpha7nAChR in EMT.

ESDR618 - Endothelial to mesenchymal transition - a novel field of action of the alpha7 nicotinic acetylcholine receptor?

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.