%0 Journal Article
%T Cycloastragenol restrains keratinocyte hyperproliferation by promoting autophagy via the miR-145/STC1/Notch1 axis in psoriasis.
%A Xia J
%A Zhang Y
%A Wang Q
%A Zhang T
%J Immunopharmacol Immunotoxicol
%V 46
%N 2
%D 2024 Apr 9
%M 38194243
%F 3.712
%R 10.1080/08923973.2023.2300310
%X <B>UNASSIGNED: </B>Psoriasis is characterized by inflammation and hyperproliferation of epidermal keratinocytes. Cycloastragenol (CAG) is an active molecule of Astragalus membranaceus that potentially plays a repressive role in psoriasis. Activated cell autophagy is an effective pathway for alleviating psoriasis progression. Thus, we investigated the role of CAG in the proliferation and autophagy of interleukin (IL)-22-stimulated keratinocytes.<BR><B>UNASSIGNED: </B>A psoriasis model was established by stimulating HaCaT cells with IL-22. Gene or protein expression levels were measured by qRT-PCR or western blot. Autophagy flux was observed with mRFP-GFP-LC3 adenovirus transfection assay under confocal microscopy. Stanniocalcin-1 (STC1) secretion levels were determined using ELISA kits. The apoptosis rate was assessed using flow cytometry. Interactions between miR-145 and STC1 or STC1 and Notch1 were validated by luciferase reporter gene assays, RIP, and Co-IP assays.<BR><B>UNASSIGNED: </B>CAG repressed cell proliferation and promoted apoptosis and autophagy in IL-22-stimulated HaCaT cells. Additionally, CAG promoted autophagy by enhancing miR-145. STC1 silencing ameliorated autophagy repression in IL-22-treated HaCaT cells. Moreover, miR-145 negatively regulated STC1, and STC1 was found to activate Notch1. Lastly, STC1 overexpression reversed CAG-promoted autophagy.<BR><B>UNASSIGNED: </B>CAG alleviated keratinocyte hyperproliferation through autophagy enhancement via regulating the miR-145/STC1/Notch1 axis in psoriasis.