Importantly, TGF-β (the main pro-fibrotic factor in SSc) suppresses the expression of HO-1 by displacing the nuclear erythroid-derived 2 (Nrf-2) transcription factor from the promoter of HO-1 (Okita et al., 2013), however this mechanism has not been explored either in early phases of SSc nor in SSc-PAH. This evidence concerns the gene HMOX1 and pulmonary arterial hypertension.