Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet.
Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet.
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DOI：
10.3389/fcimb.2023.1267629
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发表时间：
2023
影响因子：
5.7
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中科院分区：
文献类型：
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果子狸(Paguma Larvata)是将弓形虫等病原体传播给人类的蓄水池。然而，弓形虫感染果子狸的致病机制还没有被探索。我们研究了慢性感染弓形虫ME49的果子狸脑组织中的分子变化。利用iTRAQ和生物信息学研究脑组织中差异表达的蛋白质。共鉴定出268个差异蛋白，其中111个上调，157个下调。KEGG分析鉴定了PI3K-Akt信号通路、肿瘤中的蛋白多糖、碳代谢、T细胞受体信号通路。结合转录学和蛋白质组学数据，我们确定了24个在mRNA和蛋白质水平上存在差异表达的基因。免疫印迹和免疫组织化学结果证实，上调蛋白的前4位是REEP3、REEP4、TEP1和EEPD1。对这24个基因的KEGG分析确定了与小细胞肺癌、乳腺癌、Toll样受体信号通路、Wnt信号通路等相关的信号级联。为了了解观察到的变化的机制，我们使用TIMER数据库进行了免疫渗透分析，该数据库确定了与这些蛋白上调相关的免疫细胞。蛋白质网络分析确定了44个与这四个蛋白质密切相关的蛋白质。这些蛋白在免疫调节和肿瘤通路中显著丰富，包括PI3K-Akt信号通路、Notch信号通路、趋化因子信号通路、细胞周期、乳腺癌和前列腺癌。生物信息学利用两个癌症数据库(TCGA和GEPIA)显示，这四个基因在包括胶质母细胞瘤(GBM)在内的许多癌症类型中上调。此外，在GBM患者中，REEP3和EEPD1的高表达与预后良好相关，而REEP4和TEP1的高表达与预后不良相关。我们鉴定了感染弓形虫的果子狸大脑中的差异表达基因。这些基因与各种细胞信号通路有关，包括那些与免疫和癌症相关的信号通路。
The masked palm civet (Paguma larvata) serves as a reservoir in transmitting pathogens, such as Toxoplasma gondii, to humans. However, the pathogenesis of T. gondii infection in masked palm civets has not been explored. We studied the molecular changes in the brain tissue of masked palm civets chronically infected with T. gondii ME49. The differentially expressed proteins in the brain tissue were investigated using iTRAQ and bioinformatics. A total of 268 differential proteins were identified, of which 111 were upregulated and 157 were downregulated. KEGG analysis identified pathways including PI3K-Akt signaling pathway, proteoglycans in cancer, carbon metabolism, T-cell receptor signaling pathway. Combing transcriptomic and proteomics data, we identified 24 genes that were differentially expressed on both mRNA and protein levels. The top four upregulated proteins were REEP3, REEP4, TEP1, and EEPD1, which was confirmed by western blot and immunohistochemistry. KEGG analysis of these 24 genes identified signaling cascades that were associated with small cell lung cancer, breast cancer, Toll-like receptor signaling pathway, Wnt signaling pathways among others. To understand the mechanism of the observed alteration, we conducted immune infiltration analysis using TIMER databases which identified immune cells that are associated with the upregulation of these proteins. Protein network analysis identified 44 proteins that were in close relation to all four proteins. These proteins were significantly enriched in immunoregulation and cancer pathways including PI3K-Akt signaling pathway, Notch signaling pathway, chemokine signaling pathway, cell cycle, breast cancer, and prostate cancer. Bioinformatics utilizing two cancer databases (TCGA and GEPIA) revealed that the four genes were upregulated in many cancer types including glioblastoma (GBM). In addition, higher expression of REEP3 and EEPD1 was associated with better prognosis, while higher expression of REEP4 and TEP1 was associated with poor prognosis in GBM patients. We identified the differentially expressed genes in the brain of T. gondii infected masked palm civets. These genes were associated with various cellular signaling pathways including those that are immune- and cancer-related.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
6.4
作者：
Hodge, James M.;Coghill, Anna E.;Egan, Kathleen M.
通讯作者：
Egan, Kathleen M.
影响因子：
3.7
作者：
Chloe Li KY;Cook AC;Lovering RC
通讯作者：
Lovering RC
影响因子：
12.8
作者：
Hellmark, Thomas;Segelmark, Marten
通讯作者：
Segelmark, Marten
影响因子：
5.5
作者：
Gangwani, Karishma;Snigdha, Kirti;Kango-Singh, Madhuri
通讯作者：
Kango-Singh, Madhuri