S1PR1 and systemic sclerosis: In view of the ubiquitous function of S1P/S1PR1/eNOS signaling in the vasculature, the established role of S1P/S1PR2 signaling in PASMC proliferation, contraction, and the development of PH, and the specific contribution of S1PR2 and S1PR3 to disease-related extracellular matrix deposition and tissue fibrosis, we speculated that any alterations to the function of one of these three S1PR may be associated with SSc, in particular with respect to PAH development.