细胞外基质
特发性肺纤维化
病理
肌成纤维细胞
寻常性间质性肺炎
激光捕获显微切割
纤维化
肺纤维化
化学
成纤维细胞
肺
生物
细胞生物学
医学
内科学
基因表达
生物化学
体外
基因
作者
Jeremy Herrera,Lewis Dingle,M Angeles Montero Fernandez,Rajamiyer Venkateswaran,John Blaikley,Craig Lawless,Martin A. Schwartz
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2022-08-22
卷期号:7 (16)
被引量:8
标识
DOI:10.1172/jci.insight.156115
摘要
Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subjected to qualitative and quantitative analysis and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared with the nonfibrotic control. Furthermore, FF were positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of FF was predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that FF are the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This essential information will inform future mechanistic studies on fibrosis progression.
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