Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.

Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.
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DOI:
10.1016/j.cellimm.2018.01.002
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发表时间:
2018-03
影响因子:
4.3
通讯作者:
Atamas SP
Atamas SP
中科院分区:
医学4区
文献类型:
--
作者:
Luzina IG;Salcedo MV;Rojas-Peña ML;Wyman AE;Galvin JR;Sachdeva A;Clerman A;Kim J;Franks TJ;Britt EJ;Hasday JD;Pham SM;Burke AP;Todd NW;Atamas SP

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特发性肺纤维化(IPF)是一种致命的肺部疾病,表现为明显疤痕的外周和基底区域以及外观更为正常的中央肺区域。通过 RNASeq 分析来自外植 IPF 肺的宏观正常 (IPFn) 和疤痕 (IPF) 区域的肺组织,并与健康对照 (HC) 肺组织进行比较。与 HC 组织相比,IPFn 存在深刻的转录组变化,其中包括许多免疫、炎症和细胞外基质相关 mRNA 的表达升高,这些变化与 IPF 与 HC 相比观察到的变化相似。直接将 IPFn 与 IPF 进行比较,在 IPF 组织中观察到上皮粘液纤毛 mRNA 的表达升高。因此,尽管 IPF 存在已知的地理组织异质性,但整个肺部积极参与疾病过程,并表现出许多免疫相关基因的表达显着升高。因此,正常组织和疤痕组织之间的差异可能是由上皮稳态紊乱或可能的非转录组因素造成的。
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease manifested by overtly scarred peripheral and basilar regions and more normal-appearing central lung areas. Lung tissues from macroscopically normal-appearing (IPFn) and scarred (IPFs) areas of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of numerous immune-, inflammation-, and extracellular matrix-related mRNAs, and these changes were similar to those observed with IPFs compared to HC. Comparing IPFn directly to IPFs, elevated expression of epithelial mucociliary mRNAs was observed in the IPFs tissues. Thus, despite the known geographic tissue heterogeneity in IPF, the entire lung is actively involved in the disease process, and demonstrates pronounced elevated expression of numerous immune-related genes. Differences between normal-appearing and scarred tissues may thus be driven by deranged epithelial homeostasis or possibly non-transcriptomic factors.
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