Inhibition of HaCaT Proliferation and Imiquimod-Induced Psoriasis by Calcipotriol Through Regulation of the Glutathione/Glutathione Peroxidase 4 Pathway

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-02-01 DOI:10.1166/jbn.2024.3777

Lei Yang, Yue Zhang, Jiansong Wu, Lei Wang, Shan Liu, Li Zhou, Jigang Zhang, Chengxin Li

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引用次数: 0

Abstract

Psoriasis is a chronic and recurrent skin disease characterized by aberrant proliferation and differentiation of keratinocyte cells. Although calcipotriol has been employed in the clinical management of psoriasis, no association between the anti-inflammatory mechanism and iron death has been reported. Therefore, we assume that calcipotriol may down-regulate cell activity and suppress the expression of tissue inflammatory factors by regulating the glutathione (GSH) and glutathione peroxidase 4 (GPX4) pathway, thereby alleviating tissue inflammation and ameliorating psoriasis symptoms. The experimental groups consisted of a control group, a model group, a Calcipotriol group, and a Calcipotriol+Ferrostatin-1 group. In vitro experiments, a lipopolysaccharides-induced HaCaT cell model was established. In vivo experiments, an imiquimod-induced psoriasis mice model was constructed. The results showed that calcipotriol effectively downregulated the expression of GPX4 and GSH, thereby inhibiting HaCaT cell proliferation through modulation of Ki-67 protein expression and DNA breakage. Ferrostatin-1 could partially reverse these effects. Additionally, calcipotriol downregulated the expression of GPX4 and GSH in skin tissues and upregulated the expression of long-chain acyl-CoA synthetase 4 by suppressing the levels of SLC7A11 and ferritin, leading to promote the accumulation of ROS and ferroptosis. Moreover, calcipotriol demonstrated inhibitory effects on the inflammatory mediators and attenuated skin inflammation. Therefore, calcipotriol effectively ameliorated psoriatic lesions. In conclusion, this study revealed that calcipotriol exerts its therapeutic potential by promoting cellular clearance and suppressing tissue inflammation through upregulation of ferroptosis progression. Therefore, this study provides new therapeutic drugs and functions for the treatment of psoriasis.

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卡泊三醇通过调节谷胱甘肽/谷胱甘肽过氧化物酶 4 通路抑制 HaCaT 增殖和咪喹莫特诱导的牛皮癣

银屑病是一种慢性复发性皮肤病，其特征是角质形成细胞的异常增殖和分化。虽然钙泊三醇已被用于银屑病的临床治疗，但还没有关于抗炎机制与铁死亡之间的关联的报道。因此，我们推测钙泊三醇可能通过调节谷胱甘肽（GSH）和谷胱甘肽过氧化物酶 4（GPX4）途径，下调细胞活性并抑制组织炎症因子的表达，从而缓解组织炎症并改善银屑病症状。实验组包括对照组、模型组、钙泊三醇组和钙泊三醇+前列素-1组。在体外实验中，建立了脂多糖诱导的 HaCaT 细胞模型。在体内实验中，建立了咪喹莫特诱导的银屑病小鼠模型。结果表明，钙泊三醇能有效降低 GPX4 和 GSH 的表达，从而通过调节 Ki-67 蛋白表达和 DNA 断裂抑制 HaCaT 细胞的增殖。铁前列素-1 可以部分逆转这些影响。此外，钙泊三醇通过抑制 SLC7A11 和铁蛋白的水平，下调了皮肤组织中 GPX4 和 GSH 的表达，并上调了长链酰基-CoA 合成酶 4 的表达，从而促进了 ROS 的积累和铁变态反应。此外，钙泊三醇还能抑制炎症介质，减轻皮肤炎症。因此，钙泊三醇能有效改善银屑病皮损。总之，本研究揭示了钙泊三醇通过上调铁氧化酶的进展，促进细胞清除和抑制组织炎症，从而发挥其治疗潜力。因此，本研究为治疗银屑病提供了新的治疗药物和功能。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.