Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats.
Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats.
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DOI：
10.1177/15593258221104609
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发表时间：
2022-04
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阐明放射性食管损伤（RIEI）发生和发展的分子机制对于预防和治疗具有重要意义。尽管不断取得进展，但控制RIEI的潜在机制在很大程度上仍然未知。在本研究中，进行RNA-seq来表征暴露于0、25或35戈伊辐射的辐射大鼠食管的mRNA谱。进行生物信息学分析，包括剂量依赖性差异表达基因（DEG），基因本体论（GO），基因和基因组的京都百科全书（KEGG）途径，蛋白质-蛋白质相互作用（PPI）网络，和免疫浸润。筛选出134个DEG，且呈剂量依赖关系（35戈伊> 25戈伊>对照，或35戈伊< 25戈伊<对照）。GO和KEGG分析表明，最重要的机制是IL-17信号介导的炎症反应。通过参与炎症反应的DEG、IL-17通路和PPI网络的交叉，鉴定了5个中枢基因，Ccl 11、Cxcl 3、Il 17 a、S100 a8和S100 a9。此外，免疫浸润分析显示巨噬细胞、单核细胞、T细胞、NKT细胞和中性粒细胞的活化，其中巨噬细胞、单核细胞和中性粒细胞可能是S100 a8和S100 a9的主要来源。因此，这些发现进一步加深了我们对RIEI分子生物学的理解，并可能有助于开发更有效的治疗策略。
Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies.