%0 Journal Article
%T Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.
%A Slominski AT
%A Kim TK
%A Janjetovic Z
%A Slominski RM
%A Li W
%A Jetten AM
%A Indra AK
%A Mason RS
%A Tuckey RC
%J J Invest Dermatol
%V 0
%N 0
%D 2024 Jul 11
%M 39001720
%F 7.59
%R 10.1016/j.jid.2024.04.022
%X 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.