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环孢素 A 在人真皮成纤维细胞中的作用机制-转录组分析。

Potential Mechanism of Action of Cyclosporin A in Human Dermal Fibroblasts-Transcriptomic Analysis of .

机构信息

Department of Analytical Chemistry, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.

Department of Molecular Biology, Medical University of Silesia, Jedności 8, 41-200 Sosnowiec, Poland.

出版信息

Molecules. 2018 Jul 5;23(7):1642. doi: 10.3390/molecules23071642.

Abstract

Effect of cyclosporin A (CsA) in a therapeutic concentration, on the expression of cytochrome P450 genes (), was investigated in normal human dermal fibroblast cells. The expression of 57 genes, encoding cytochrome P450 isoforms, was estimated using the microarray method. Amongst 396 normalized fluorescence signals related to cytochrome P450 activity, only 91 were strictly connected to and were analyzed using two methods: a self-organizing feature map of artificial neural networks and typical statistical analysis with significance level at ≤ 0.05. Comparing the samples from fibroblasts cultured with CsA and those cultured without, up-regulated changes of , , , , and down-regulated gene expression were observed. The mRNAs with increased changes were in the same neuron of the self-organizing feature map. All distinguished encode monooxygenases, which plays an important role in steroids biosynthesis and metabolism. Based on the obtained results, we can conclude that CsA in therapeutic concentration changes the expression profile of in human dermal fibroblasts, especially affecting genes linked to steroids synthesis and/or metabolism. It shows the potential mechanism of action of CsA in human dermal fibroblast cells.

摘要

研究了环孢素 A(CsA)在治疗浓度下对正常人皮肤成纤维细胞细胞色素 P450 基因()表达的影响。使用微阵列方法估计了编码细胞色素 P450 同工酶的 57 个基因的表达。在与细胞色素 P450 活性相关的 396 个归一化荧光信号中,仅与 严格相关的 91 个信号使用两种方法进行了分析:人工神经网络的自组织特征映射和具有统计学意义的典型分析(≤0.05)。将用 CsA 培养的成纤维细胞样本与未用 CsA 培养的成纤维细胞样本进行比较,观察到 、 、 、 、 和 基因表达下调。变化增加的 mRNA 位于自组织特征映射的同一神经元中。所有区分的编码单加氧酶,在类固醇生物合成和代谢中起着重要作用。基于获得的结果,可以得出结论,治疗浓度的 CsA 改变了人皮肤成纤维细胞中 的表达谱,特别是影响与类固醇合成和/或代谢相关的基因。它显示了 CsA 在人皮肤成纤维细胞中的潜在作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0880/6100361/9b264e863799/molecules-23-01642-g001.jpg

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