Transcriptome Analysis Reveals Unfolded Protein Response Was Induced During the Early Stage of Burkholderia pseudomallei Infection in A549 Cells.
Transcriptome Analysis Reveals Unfolded Protein Response Was Induced During the Early Stage of Burkholderia pseudomallei Infection in A549 Cells.
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DOI：
10.3389/fgene.2020.585203
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发表时间：
2020
影响因子：
3.7
通讯作者：
Liao Y
中科院分区：
文献类型：
--
作者：
Rao C;Mao C;Xia Y;Zhang M;Hu Z;Yuan S;Yang W;Yan J;Deng L;Cai X;Mao X;Li Q;Liao Y
假鼻疽伯克霍尔德氏菌是一种人畜共患病原体，通常会影响患者的肺部，并导致严重的类鼻疽病。假单胞菌与宿主的相互作用是复杂的，人类对假单胞菌感染的细胞反应仍有待阐明。在这项研究中，通过转录转录图谱分析了假鼻疽杆菌感染的人肺上皮细胞A549在早期感染(EI)阶段的细胞反应动力学。使用在线数据库David 6.8和Kobas 3.0进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径分析。采用实时荧光定量聚合酶链式反应和免疫印迹方法进行验证实验。与阴性对照组(NC)相比，一组36个共同基因随着时间的推移而变化，其截止水平变化了1.5倍，并被鉴定为P值<；0.05。生物信息学分析表明，PERK介导的未折叠蛋白反应(UPR)是最值得关注的生物过程类别，它作为UPR的一个分支，在内质网蛋白质加工的信号通路中得到了丰富。其他类别，如炎症反应、细胞迁移和细胞凋亡，也受到关注。分子伴侣Bip(GRP78)、PERK和PERK传感器依赖的eIF2α和ATF4的磷酸化(p-eIF2ATF4)在EI阶段随着时间的推移而增加，提示假鼻疽杆菌感染激活了PERK介导的A549细胞的UPR。综上所述，这些结果为了解假腮腺炎杆菌与肺上皮细胞之间的密切相互作用提供了重要的初步见解，可以进一步探索人类感染假腮腺炎杆菌的细胞机制。
Burkholderia pseudomallei is a zoonotic pathogen that usually affects patients' lungs and causes serious melioidosis. The interaction of B. pseudomallei with its hosts is complex, and cellular response to B. pseudomallei infection in humans still remains to be elucidated. In this study, transcriptomic profiling of B. pseudomallei-infected human lung epithelial A549 cells was performed to characterize the cellular response dynamics during the early infection (EI) stage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the online databases DAVID 6.8 and KOBAS 3.0. Real-time quantitative PCR and western blot were used for validation experiments. Compared with the negative control group (NC), a set of 36 common genes varied over time with a cut-off level of 1.5-fold change, and a P-value < 0.05 was identified. Bioinformatics analysis indicated that the PERK-mediated unfolded protein response (UPR) was enriched as the most noteworthy biological process category, which was enriched as a branch of UPR in the signaling pathway of protein processing in the endoplasmic reticulum. Other categories, such as inflammatory responses, cell migration, and apoptosis, were also focused. The molecular chaperone Bip (GRP78), PERK, and PERK sensor-dependent phosphorylation of eIF2α (p-eIF2α) and ATF4 were verified to be increasing over time during the EI stage, suggesting that B. pseudomallei infection activated the PERK-mediated UPR in A549 cells. Collectively, these results provide important initial insights into the intimate interaction between B. pseudomallei and lung epithelial cells, which can be further explored toward the elucidation of the cellular mechanisms of B. pseudomallei infections in humans.
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影响因子：
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作者：
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