The “HIF-1 Signalling Pathway” includes gene encoding proteins, mediating adaptive responses to nitric oxide and reduced oxygen availability, a common condition during SSc, in which a desertification of vascular tree is present, and it is not surprising to observe that the validated target genes for this pathway are: PLCG1, FLT1 and EIF4E2, which may mediate MSCs proliferation, angiogenesis and survival in hypoxia condition38,43,44, suggesting a compensatory mechanism in these patients. This evidence concerns the gene PLCG1 and systemic sclerosis.