Epigenetic regulation constitutes another important layer, as hypermethylation‐driven downregulation of SFRP1 or SFRP5 in fibrotic tissues (e.g., skin, lung, kidney, and SSc) reduces their antifibrotic potential and skews Wnt pathway activity [233, 234, 235, 236, 237, 238, 239]. This evidence concerns the gene SFRP1 and systemic sclerosis.