{"title":"Cycloastragenol restrains keratinocyte hyperproliferation by promoting autophagy via the miR-145/STC1/Notch1 axis in psoriasis.","authors":"Jie Xia, Yuan Zhang, Qing Wang, Teng Zhang","doi":"10.1080/08923973.2023.2300310","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is characterized by inflammation and hyperproliferation of epidermal keratinocytes. Cycloastragenol (CAG) is an active molecule of <i>Astragalus membranaceus</i> 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>CAG alleviated keratinocyte hyperproliferation through autophagy enhancement <i>via</i> regulating the miR-145/STC1/Notch1 axis in psoriasis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"229-239"},"PeriodicalIF":2.9000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunopharmacology and Immunotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08923973.2023.2300310","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/9 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: CAG alleviated keratinocyte hyperproliferation through autophagy enhancement via regulating the miR-145/STC1/Notch1 axis in psoriasis.
期刊介绍：
The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal.
The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome.
With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more.
Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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