{Reference Type}: Journal Article {Title}: Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin. {Author}: Slominski AT;Kim TK;Janjetovic Z;Slominski RM;Li W;Jetten AM;Indra AK;Mason RS;Tuckey RC; {Journal}: J Invest Dermatol {Volume}: 0 {Issue}: 0 {Year}: 2024 Jul 11 {Factor}: 7.59 {DOI}: 10.1016/j.jid.2024.04.022 {Abstract}: Novel pathways of vitamin D3, lumisterol 3 (L3), and tachysterol 3 (T3) activation have been discovered, initiated by CYP11A1 and/or CYP27A1 in the case of L3 and T3. The resulting hydroxymetabolites enhance protection of skin against DNA damage and oxidative stress; stimulate keratinocyte differentiation; exert anti-inflammatory, antifibrogenic, and anticancer activities; and inhibit cell proliferation in a structure-dependent manner. They act on nuclear receptors, including vitamin D receptor, aryl hydrocarbon receptor, LXRα/β, RAR-related orphan receptor α/γ, and peroxisome proliferator-activated receptor-γ, with selectivity defined by their core structure and distribution of hydroxyl groups. They can activate NRF2 and p53 and inhibit NF-κB, IL-17, Shh, and Wnt/β-catenin signaling. Thus, they protect skin integrity and physiology.