Changes in mRNA expression precede changes in microRNA expression in lesional psoriatic skin during treatment with adalimumab
Changes in mRNA expression precede changes in microRNA expression in lesional psoriatic skin during treatment with adalimumab
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DOI：
10.1111/bjd.13721
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发表时间：
2015-08-01
影响因子：
10.3
通讯作者：
Iversen, L.
中科院分区：
文献类型：
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作者：
Raaby, L.;Langkilde, A.;Iversen, L.
背景肿瘤坏死因子（TNF）-α抑制是中重度斑块型银屑病的有效治疗方法。治疗4天后，在任何临床或组织学改善之前，皮肤中细胞因子表达谱发生变化。microRNAs（miRNAs）是基因表达的重要转录后调节因子，目的研究阿达木单抗治疗期间银屑病皮肤中miRNA表达的变化，并将结果与Aldara诱导的银屑病小鼠模型中miRNA表达的变化进行比较。方法在阿达木单抗治疗期间从非病灶和病灶银屑病皮肤获得打孔活检。在Aldara诱导的皮肤炎症小鼠模型中，从TNF-α敲除（KO）、IL-17 A KO和野生型小鼠中获得活检。用微阵列、逆转录定量聚合酶链反应（RT-PCR）和原位杂交（in-situ hybridization.Results）分析银屑病患者皮肤中miRNA的表达水平。治疗14天后，几种miRNA的表达朝着治疗前在非病变皮肤中观察到的水平标准化。miR-23 b表达在治疗14天后增加，并在84天内保持高水平，尽管基线水平不变。在阿达木单抗诱导的小鼠皮肤炎症模型中，miR-146 a的表达水平升高，而miR-203、miR-214- 3 p、miR-125 a、miR-23 b和let-7 d-5 p的表达水平未受到调节。结论阿达木单抗治疗4 d后，细胞因子表达水平的变化并不受早期miRNA表达变化的影响。
Background Tumour necrosis factor (TNF)-alpha inhibition is an effective treatment for moderate to severe plaque-type psoriasis. A change in the cytokine expression profile occurs in the skin after 4 days of treatment, preceding any clinical or histological improvements. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, but miRNA expression has never been studied in psoriatic skin during treatment.Objective To investigate changes in miRNA expression in psoriatic skin during adalimumab treatment and to compare results with changes in miRNA expression in a mouse model of Aldara-induced psoriasis-like skin inflammation.Methods Punch biopsies were obtained from nonlesional and lesional psoriatic skin during adalimumab treatment. In the mouse model of Aldara-induced skin inflammation, biopsies were obtained from TNF-alpha knockout (KO), IL-17A KO and wildtype mice. miRNA expression levels were analysed with microarray, reverse transcriptase quantitative polymerase chain reaction and in situ hybridization.Results In psoriatic skin, no changes in miRNA expression were seen 4 days after treatment initiation. After 14 days of treatment, the expression of several miRNAs was normalized towards the level seen in nonlesional skin before treatment. miR-23b expression increased after 14 days of treatment and remained high for 84 days, despite unaltered levels at baseline. In the mouse model of Aldara-induced skin inflammation, the level of miR-146a increased, whereas no regulation was seen for miR-203, miR-214-3p, miR-125a, miR-23b or let-7d-5p.Conclusions This study demonstrates that the changes seen in the cytokine expression levels after 4 days of treatment with adalimumab are not facilitated by early changes in miRNA expression.