To unravel the underlying mechanism of action of CYP11A1-derived vitamin D3 hydroxymetabolites in fibrosis, we investigated the involvement of the VDR- and ROR-dependent pathways, and tested whether CYP27B1 is necessary to activate the two secosteroids lacking a C1α-hydroxyl group, namely 20(OH)D3 and 20,23(OH)2D3. This evidence concerns the gene CYP27B1 and fibrosis.