unilateral-lung-volume-analysis-using-micro-ct-for-enhanced

Unilateral Lung Volume Analysis Using Micro-CT for Enhanced Assessment of Pulmonary Fibrosis in Preclinical Models

Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease characterized by poor prognosis and limited treatment options. The ...

orthotopic-left-lung-transplantation-in-rats

Orthotopic Left Lung Transplantation in Rats

The rat left lung orthotopic transplantation model is an essential tool in lung transplant research. Although lung transplantation is a complex procedure, ...

establishment-evaluation-an-vitro-human-based-advanced-model

Establishment and Evaluation of an <em>In Vitro</em> Human-Based Advanced Model of Pulmonary Fibrosis

Pulmonary fibrosis is characterized by irreversible destruction of alveolar structure and excessive deposition of extracellular matrix. Although animal ...

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou Medical University

Andrographolide (Andro), a diterpenoid extracted from , has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear. This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells.

Andrographolide alleviates bleomycin-induced NLRP3 inflammasome activation and epithelial-mesenchymal transition in lung epithelial cells by suppressing AKT/mTOR signaling pathway.

 Sustained activation of lung fibroblasts and the resulting oversynthesis 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, and is also 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 or 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 first tested using multiple experimental methods, including real-time quantitative PCR (qPCR), Western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry, as well as single-cell sequencing. In addition, FAP-targeted positron emission tomography/computed tomography imaging PET/CT was applied to various types of patients with ILD, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed.  Here, it was revealed, for the first time, FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of profibrotic 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 standard uptake value (SUV) of FAP inhibitor (FAPI) PET (SUVtotal) was significantly related to lung function decline in patients with ILD.  Our results strongly support that  and  detection of FAP can assess the profibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window.

Comprehensive Analysis of Fibroblast Activation Protein Expression in Interstitial Lung Diseases.

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease with limited therapeutic options and high lethality, related to alveolar type II epithelial (ATII) cell dysregulation, the abnormal repair of alveolar epithelial cells and activation of fibroblasts promote the development of pulmonary fibrosis. Fatty acid binding protein 1 (FABP1) was significantly downregulated in the fibrotic state by proteomics screening in our previous date, and the ATII cell dysregulation can be mediated by FABP1 via regulating fatty acid metabolism and intracellular transport. The aim of this study was to evaluate the role and potential mechanism of FABP1 in the development of pulmonary fibrosis.

Therapeutic effects of fatty acid binding protein 1 in mice with pulmonary fibrosis by regulating alveolar epithelial regeneration.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies has impelled researchers to reconsider the importance of the choice of animal model and assessment methodologies. Currently, it is still not settled whether the bleomycin-induced lung fibrosis mouse model finally returns to resolution.

ArticleTotal : 3	Year
Publication title	2025
Publication title Cited by 1	2025
Publication title	2025

Article	Year
Andrographolide alleviates bleomycin-induced NLRP3 inflammasome activation and epithelial-mesenchymal transition in lung epithelial cells by suppressing AKT/mTOR signaling pathway. Annals of translational medicine\| PubMed ID: 34268377	2021
Comprehensive Analysis of Fibroblast Activation Protein Expression in Interstitial Lung Diseases. American journal of respiratory and critical care medicine\| PubMed ID: 35984444	2023
Therapeutic effects of fatty acid binding protein 1 in mice with pulmonary fibrosis by regulating alveolar epithelial regeneration. BMJ open respiratory research\| PubMed ID: 37940355	2023
Intracellular hydroxyproline imprinting following resolution of bleomycin-induced pulmonary fibrosis. The European respiratory journal\| PubMed ID: 34561295	2022

Penghui Yang

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