Transcriptome Sequencing Reveals the Mechanism behind Chemically Induced Oral Mucositis in a 3D Cell Culture Model.

Transcriptome Sequencing Reveals the Mechanism behind Chemically Induced Oral Mucositis in a 3D Cell Culture Model.
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转录组测序揭示了3D细胞培养模型中化学诱导口腔粘膜炎的机制。

DOI:
10.3390/ijms24055058
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发表时间:
2023-03-06
影响因子:
5.6
通讯作者:
Van Haute, Lindsey
Van Haute, Lindsey
中科院分区:
生物学2区
文献类型:
--
作者:
Lambros, Maria;Moreno, Jonathan;Fei, Qinqin;Parsa, Cyrus;Orlando, Robert;Van Haute, Lindsey

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口腔黏膜炎是癌症治疗的常见副作用,特别是用mTORC1抑制剂依维莫司治疗。目前的治疗方法还不够有效,有必要更好地了解口腔黏膜炎的原因和机制,以找到潜在的治疗靶点。在这里,我们用高剂量或低剂量的依维莫司处理了一个由在人成纤维细胞上生长的人角质形成细胞组成的器官型3D口腔粘膜组织模型40或60小时,并研究了(1)依维莫司对3D细胞培养的显微镜切片的影响,以证明形态学变化;(2)通过高通量RNA-Seq分析转录组的变化。我们发现最受影响的途径是玉米化、细胞因子表达、糖酵解和细胞增殖,并提供了进一步的细节。本研究为更好地了解口腔黏膜炎的发生发展提供了良好的资源。它给出了参与粘膜炎的不同分子途径的详细概述。这反过来又提供了潜在治疗靶点的信息,这是预防或控制癌症治疗常见副作用的重要一步。
Oral mucositis is a common side effect of cancer treatment, and in particular of treatment with the mTORC1 inhibitor everolimus. Current treatment methods are not efficient enough and a better understanding of the causes and mechanisms behind oral mucositis is necessary to find potential therapeutic targets. Here, we treated an organotypic 3D oral mucosal tissue model consisting of human keratinocytes grown on top of human fibroblasts with a high or low dose of everolimus for 40 or 60 h and investigated (1) the effect of everolimus on microscopic sections of the 3D cell culture for evidence of morphologic changes and (2) changes in the transcriptome by high throughput RNA-Seq analysis. We show that the most affected pathways are cornification, cytokine expression, glycolysis, and cell proliferation and we provide further details. This study provides a good resource towards a better understanding of the development of oral mucositis. It gives a detailed overview of the different molecular pathways that are involved in mucositis. This in turn provides information about potential therapeutic targets, which is an important step towards preventing or managing this common side effect of cancer treatment.
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发表时间: 2016-09-15
期刊: BIOINFORMATICS
影响因子: 5.8
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发表时间: 2016-05-02
影响因子: 5.4
作者:
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