Comparison of temporal transcriptomic profiles from immature lungs of two rat strains reveals a viral response signature associated with chronic lung dysfunction.
Comparison of temporal transcriptomic profiles from immature lungs of two rat strains reveals a viral response signature associated with chronic lung dysfunction.
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DOI：
10.1371/journal.pone.0112997
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lemanske RF Jr
中科院分区：
文献类型：
--
作者：
Hines EA;Szakaly RJ;Leng N;Webster AT;Verheyden JM;Lashua AJ;Kendziorski C;Rosenthal LA;Gern JE;Sorkness RL;Sun X;Lemanske RF Jr
生命早期呼吸道病毒感染和特应性特征是儿童哮喘发生的重要危险因素。据推测，反复呼吸道病毒感染可能通过干扰肺成熟的正常过程来诱导结构重塑；然而，这些病理变化背后的具体分子过程尚不清楚。为了研究这些变化的分子基础，我们在断奶大鼠中使用了已建立的仙台病毒感染模型，比较了特应性哮喘易感株 Brown挪威和非特应性哮喘耐药株 Fischer 344 的感染后转录组。特定于这种断奶感染模型且在成人感染模型中没有描述，易感株而非耐药株中的仙台病毒会导致远端气道的形态异常，并持续到成年期。五个时间点的感染肺和对照肺的基因表达数据表明，与 Fischer 344 大鼠相比，Brown挪威大鼠肺中病毒感染后免疫反应的具体特征增强并延长。这些特征包括巨噬细胞数量和相关基因表达的增加，然后转变为肥大细胞数量和相关基因表达的增加。相比之下，受感染的 Fischer F344 肺表现出更有效的气道上皮形态恢复，在远端气道附近短暂出现基底细胞荚。总之，这些发现表明，显着的巨噬细胞和肥大细胞反应以及异常的上皮再形成先于布朗挪威肺中出现和持续的结构缺陷，但 Fischer 344 肺中则不然。
Early life respiratory viral infections and atopic characteristics are significant risk factors for the development of childhood asthma. It is hypothesized that repeated respiratory viral infections might induce structural remodeling by interfering with the normal process of lung maturation; however, the specific molecular processes that underlie these pathological changes are not understood. To investigate the molecular basis for these changes, we used an established Sendai virus infection model in weanling rats to compare the post-infection transcriptomes of an atopic asthma susceptible strain, Brown Norway, and a non-atopic asthma resistant strain, Fischer 344. Specific to this weanling infection model and not described in adult infection models, Sendai virus in the susceptible, but not the resistant strain, results in morphological abnormalities in distal airways that persist into adulthood. Gene expression data from infected and control lungs across five time points indicated that specific features of the immune response following viral infection were heightened and prolonged in lungs from Brown Norway rats compared with Fischer 344 rats. These features included an increase in macrophage cell number and related gene expression, which then transitioned to an increase in mast cell number and related gene expression. In contrast, infected Fischer F344 lungs exhibited more efficient restoration of the airway epithelial morphology, with transient appearance of basal cell pods near distal airways. Together, these findings indicate that the pronounced macrophage and mast cell responses and abnormal re-epithelialization precede the structural defects that developed and persisted in Brown Norway, but not Fischer 344 lungs.
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影响因子：
8
作者：
通讯作者：
--
影响因子：
15.9
作者：
Dunsmore, SE;Saarialho-Kere, UK;Parks, WC
通讯作者：
Parks, WC
影响因子：
5.8
作者：
Becnel, D;You, DH;Cormier, SA
通讯作者：
Cormier, SA
影响因子：
6.1
作者：
Hizawa, N.;Maeda, Y.;Nishimura, M.
通讯作者：
Nishimura, M.
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP