Studies show that HMECs stimulated by SSc-IgG-related antibodies activate PAR-1, thus initiating a signalling sequence that involves the phosphatidylinositol-3-kinase/mammalian target of the rapamycin/extracellular signal-regulated kinases 1/2 (PI3K/mTOR/ERK1/2) pathway and the activator protein 1/c-FOS (AP-1/c-FOS) transcription factor. This evidence concerns the gene MAPK3 and systemic sclerosis.