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维胺酯通过调控 S100A8/S100A9-MAPK 级联抑制痤疮丙酸杆菌诱导的 HaCat 细胞异常增殖和角化。

Viaminate Inhibits Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.

机构信息

Department of Dermatology, the Second Affiliated Hospital of Xi 'an Jiaotong University, 157 Xiwu Road, Xi 'an City 710103, Shaanxi Province, China.

出版信息

Curr Drug Targets. 2023;24(13):1055-1065. doi: 10.2174/0113894501243867230928115205.

Abstract

BACKGROUND

Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown.

METHODS

In the present study, acne was induced in the ears of rats using acnes combined with sebum application.

RESULTS

After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models.

CONCLUSION

In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

摘要

背景

维胺酯,中国研发的维 A 酸类药物,已在临床上用于治疗痤疮,调节上皮细胞分化和增殖,抑制角化,减少皮脂分泌,并控制免疫和抗炎作用;然而,其确切作用机制尚不清楚。

方法

本研究采用痤疮丙酸杆菌联合皮脂应用诱导大鼠耳部产生痤疮。

结果

维胺酯治疗 30 天后,大鼠耳部表皮增厚和角蛋白过度生成的症状明显改善。大鼠皮肤组织的转录组分析表明,维胺酯显著调节细胞角化的生物学途径。基因差异分析显示,维胺酯处理后 S100A8 和 S100A9 基因显著下调。qPCR 和 Western blot 结果证实,维胺酯抑制了大鼠和 HaCat 细胞痤疮模型中 S100A8 和 S100A9 基因及其蛋白的表达,同时抑制了 MAPK(MAPK p38/JNK/ERK1/2)蛋白表达水平。S100A8 和 S100A9 复合物蛋白的额外给药显著逆转了维胺酯对痤疮细胞模型中异常增殖和角化水平的抑制作用。

结论

综上所述,维胺酯通过调节 S100A8 和 S100A9 抑制 MAPK 通路激活,抑制角质形成细胞增殖和角化水平,从而改善痤疮。

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