Astragaloside IV promotes keratinocyte proliferation and migration through upregulating lncRNA H19 recruited ILF3 to enhance the stability of CDK4 mRNA.

IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Dan-Dan Wang, Li-Ze Zhang, Cheng-Jian Pang, Jian-Zhou Ye
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引用次数: 1

Abstract

Skin is the first line of the body to resist pathogen invasion. A potentially fatal infection may result from problems with wound healing. Small molecule drugs like astragaloside IV (AS-IV) show pro-healing activities, but the mechanisms are not fully understood. Using real-time quantitative PCR and a western blot assay, the amount of gene expression was evaluated. The proliferation and migration of keratinocytes were determined by MTS and wound healing assay, respectively. The binding of lncRNA H19 to RBP protein ILF3 and the binding of ILF3 protein to CDK4 mRNA were confirmed by RNA immunoprecipitation. Treatment with AS-IV enhanced the expression of lncRNA H19, ILF3, and CDK4 and improved the proliferation and migration of keratinocytes HaCaT. Additionally, apoptosis of keratinocytes was attenuated by AS-IV. Further studies showed that both lncRNA H19 and ILF3 were important for AS-IV-mediated keratinocyte growth and migration. In addition, lncRNA H19 recruited ILF3 to increase CDK4 mRNA level and enhanced cell proliferation. We discovered a lncRNA H19/ILF3/CDK4 axis that is activated by AS-IV to promote keratinocyte migration and proliferation. These results elucidate the mechanism of action of AS-IV and justify its application in further application in wound healing treatment.

黄芪甲苷通过上调lncRNA H19募集ILF3,增强CDK4 mRNA的稳定性,促进角化细胞增殖和迁移。
皮肤是人体抵抗病原体侵袭的第一道防线。伤口愈合的问题可能导致潜在的致命感染。小分子药物如黄芪甲苷(AS-IV)具有促愈合活性,但其机制尚不完全清楚。采用实时定量PCR和western blot法检测基因表达量。MTS法和创面愈合法分别测定了角质形成细胞的增殖和迁移。通过RNA免疫沉淀证实lncRNA H19与RBP蛋白ILF3结合,ILF3蛋白与CDK4 mRNA结合。AS-IV增强了lncRNA H19、ILF3和CDK4的表达,改善了角化细胞HaCaT的增殖和迁移。此外,AS-IV可减弱角质形成细胞的凋亡。进一步的研究表明,lncRNA H19和ILF3对as - iv介导的角质细胞生长和迁移都很重要。此外,lncRNA H19募集ILF3增加CDK4 mRNA水平,促进细胞增殖。我们发现了一个lncRNA H19/ILF3/CDK4轴被AS-IV激活,从而促进角质形成细胞的迁移和增殖。这些结果阐明了AS-IV的作用机制,为其在伤口愈合治疗中的进一步应用提供了依据。
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来源期刊
Kaohsiung Journal of Medical Sciences
Kaohsiung Journal of Medical Sciences 医学-医学:研究与实验
CiteScore
5.60
自引率
3.00%
发文量
139
审稿时长
4-8 weeks
期刊介绍: Kaohsiung Journal of Medical Sciences (KJMS), is the official peer-reviewed open access publication of Kaohsiung Medical University, Taiwan. The journal was launched in 1985 to promote clinical and scientific research in the medical sciences in Taiwan, and to disseminate this research to the international community. It is published monthly by Wiley. KJMS aims to publish original research and review papers in all fields of medicine and related disciplines that are of topical interest to the medical profession. Authors are welcome to submit Perspectives, reviews, original articles, short communications, Correspondence and letters to the editor for consideration.
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