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Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1

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机构: [1]Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, No.1 Dongjiaomin Lane, Dongcheng District, Beijing, 100730, China.
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关键词: Caffeic acid psoriasis keratinocytes EGR1 CHAC1

摘要:
Ferroptosis of keratinocytes is closely associated with amplification of skin inflammation in psoriasis. This study focuses on unlocking the role of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and understanding the underlying mechanistic basis.The interaction between early growth response protein 1 (EGR1) and chac glutathione specific γ‑glutamylcyclotransferase 1 (CHAC1) was predicted by bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase reported assays. Their expressions in primary human epidermal keratinocytes were altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer). Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1 in keratinocytes were analyzed by qRT-PCR or Western blot.Increased expressions of EGR1 and CHAC1 were detected in keratinocytes with Erastin treatment. CA (100 μM) antagonized Erastin (10 μM)-induced decrease in viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects. Moreover, EGR1 overexpression and CA mutually counteracted their effects on Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1 knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown and CHAC1 overexpression reversed each other's effects.CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1 to dampen inflammation of keratinocytes in psoriasis. This study providing new compounds and candidate targets for the clinical treatment of psoriasis.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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出版当年[2023]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验
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出版当年[2022]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, No.1 Dongjiaomin Lane, Dongcheng District, Beijing, 100730, China.
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通讯机构: [1]Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, No.1 Dongjiaomin Lane, Dongcheng District, Beijing, 100730, China. [*1]Department of Dermatology, Beijing Tongren Hospital, Capital Medical University,No.1 Dongjiaomin Lane, Dongcheng District, Beijing, 100730, China
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