CD146 at the Interface between Oxidative Stress and the Wnt Signaling Pathway in Systemic Sclerosis

• DOI: 10.1016/j.jid.2022.03.038
• Publication Date: 2022-06-09T19:12:25Z
• Authors: Xavier Heim; Julien Bermudez; Ahmad Joshkon; Elise Kaspi; Richard Bachelier; Marie Nollet; Mélanie Vélier; Laetitia Dou; Alexandre Brodovitch; Alexandrine Fouca...; Aurelie S. Leroyer; Audrey Benyamine; Aurélie Daumas; Brigitte Granel; Florence Sabatier; Françoise Dignat-...; Marcel Blot-Chabaud; Nathalie Bardin
• Keywords: CD146; Knockout mouse

CD146 involvement was recently described in skin fibrosis of systemic sclerosis through its regulation the Wnt pathway. Because interaction between and ROS signaling plays a major role fibrosis, we hypothesized that sclerosis, may regulate Wnt/ROS crosstalk. Using transcriptomic western blot analysis performed on wild-type or knockout mouse embryonic fibroblasts, showed procanonical hallmark absence is reversed when expression restored. We found an elevated content cells increase DNA oxidative damage sections mice compared with those mice. also increased noncanonical ligand, WNT5A, only cells. In humans, fibroblasts from patients presented higher expressed CD146, whereas control did not. Moreover, ligand were upregulated by both human fibroblasts. The bleomycin-induced WNT5A abrogated silenced. interplay regulated which promotes pathway prevents signaling, opening way for innovative therapeutic strategies.