| Autor: |
Penghui Yang, Qun Luo, Xinlu Wang, Qi Fang, Zhenli Fu, Jia Li, Yunxin Lai, Xiaobo Chen, Xin Xu, Xiaomin Peng, Kongzhen Hu, Xiaowei Nie, Shaoyu Liu, Jinhe Zhang, Junqi Li, Chenyou Shen, Yingying Gu, Jianping Liu, Jingyu Chen, Nanshan Zhong, Jin Su |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
American journal of respiratory and critical care medicine. |
| ISSN: |
1535-4970 |
| Popis: |
Sustained activation of lung fibroblasts and the resulting over-synthesis of the extracellular matrix are detrimental events for patients with interstitial lung diseases (ILDs). Lung biopsy is a primary evaluation technique for the fibrotic status of ILDs, which is a major risk factor for triggering acute deterioration. Fibroblast activation protein (FAP) is a long-known surface biomarker of activated fibroblasts, but its expression pattern and diagnostic implications in ILDs are poorly defined.The present study aims to comprehensively investigate whether the expression intensity of FAP could be used as a potential readout to estimate/measure the amounts of activated fibroblasts in ILD lungs quantitatively.FAP expression in human primary lung fibroblasts as well as in clinical lung specimens was firstly tested using multiple experimental methods, including qPCR, western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry as well as single-cell sequencing. In addition, FAP-targeted PET/CT imaging was applied to various types of ILD patients, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed.Here, it was revealed, for the first time, that FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of pro-fibrotic cytokine. Single-cell sequencing data further indicate that nearly all FAP-positive cells in ILD lungs were collagen-producing fibroblasts. Immunohistochemical analysis validated that FAP expression level was closely correlated with the abundance of fibroblastic foci on human lung biopsy sections from patients with ILDs. We found that the total uptake of FAPI PET tracer (FAPI SUVtotal) was significantly related to lung function decline in ILD patients.Our results strongly support that in vitro and in vivo detection of FAP can assess the pro-fibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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