Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.
Methods: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We compared the expression profile against control lungs (donor lungs discarded for transplantation), and explanted tissue from patients with idiopathic pulmonary fibrosis (IPF). Subsequently, RT-qPCR, Western blots and immunohistochemistry were conducted to validate and localize selected pro-fibrotic targets. A total of 23 NR-COVID-19 lungs were used for RT-qPCR validation.
Findings: We revealed a unique fibrotic gene signature in NR-COVID-19 that is dominated by a hyper-expression of pro-fibrotic genes, including collagens and periostin. Our results also show a significantly increased expression of Collagen Triple Helix Repeat Containing 1(CTHRC1) which co-localized in areas rich in alpha smooth muscle expression, denoting myofibroblasts. We also show a significant increase in cytokeratin (KRT) 5 and 8 expressing cells adjacent to fibroblastic areas and in areas of apparent epithelial bronchiolization.
Interpretation: Our studies may provide insights into potential cellular mechanisms that lead to a fulminant presentation of lung fibrosis in NR-COVID-19.
Funding: National Institute of Health (NIH) Grants R01HL154720, R01DK122796, R01DK109574, R01HL133900, and Department of Defense (DoD) Grant W81XWH2110032 to H.K.E. NIH Grants: R01HL138510 and R01HL157100, DoD Grant W81XWH-19-1-0007, and American Heart Association Grant: 18IPA34170220 to H.K.-Q. American Heart Association: 19CDA34660279, American Lung Association: CA-622265, Parker B. Francis Fellowship, 1UL1TR003167-01 and The Center for Clinical and Translational Sciences, McGovern Medical School to X.Y.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667270 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2022.104351 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development of a new alternative method to inhalation exposure: intratracheal instillation studies using molecular dispersion.
Environ Health Prev Med
September 2025
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan.
Background: Organic chemicals have been known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis; however, the possibility that they do not cause irreversible pulmonary fibrosis has not been considered. Polyacrylic acid (PAA), an organic chemical, has caused irreversible progressive pulmonary fibrosis in exposed workers, indicating its potential to induce pulmonary inflammation and fibrosis. Although intratracheal instillation studies are commonly used for evaluating lung pathology, traditional methods face challenges with chemical substances, particularly nanoparticles, which tend to aggregate in suspension and prevent uniform pulmonary distribution.
View Article and Find Full Text PDFMouse intestine as a useful model for CFTR electrophysiology function analysis.
Methods Cell Biol
September 2025
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Italy; CEINGE-Biotecnologie Avanzate, Naples, Italy.
Cystic fibrosis (CF) is a genetic disorder primarily known for its severe impact on lung function, but it also significantly affects the digestive system, leading to complications such as intestinal blockages, malabsorption, inflammation, and microbial dysbiosis. The study of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) effects on intestinal physiology is critical for developing new effective treatments. This work highlights the use of the mouse intestine as a valuable model for analyzing cellular electrophysiology and CFTR function.
View Article and Find Full Text PDFPrediabetic cardiomyopathy is attenuated by hypothalamic PVN oxytocin neuron activation.
J Physiol
September 2025
Department of Cell and Molecular Biology, University of Hawaii, Honolulu, HI, USA.
Diagnoses of prediabetes and metabolic syndromes, such as metabolic-associated steatotic liver disease (MASLD), are increasing at an alarming rate worldwide, often simultaneously. A significant consequence of these is high risk of cardiovascular disease, highlighting the need for cardiac-specific therapeutics for intervention during the prediabetic stage. Recent studies have demonstrated that chemogenetic activation of the cardiac parasympathetic system through hypothalamic oxytocin (OXT) neurons provides cardioprotective effects in heart disease models by targeting excitatory neurotransmission to brainstem cardiac vagal neurons.
View Article and Find Full Text PDFBronchiectasis in France: data on disease characteristics in 630 patients from the European Bronchiectasis registry (EMBARC).
Respir Med Res
August 2025
Cystic Fibrosis Center Service de Pneumologie Pôle des Voies Respiratoires, Hôpital Larrey CHU de Toulouse, Toulouse, France.
Background: Little is known about the characteristics of adults with bronchiectasis in France.
Methods: A descriptive cross-sectional study was conducted to describe the characteristics of adults (≥18 years) with clinically-significant bronchiectasis, diagnosed on a combination of respiratory symptoms and CT scan findings, and followed in 18 participating centers. Data on, etiology, lung function, symptoms, microbiology, treatments and quality of life were collected.
Metformin attenuates coal dust nanoparticle-induced pulmonary fibrosis by modulating inflammation and epithelial-mesenchymal transition.
Int Immunopharmacol
September 2025
The First Hospital of Anhui University of Science and Technology, Huainan 232000, China; Bengbu Medical University, Bengbu 233030, China. Electronic address:
Coal worker pneumoconiosis is an occupational pulmonary fibrosis (PF) caused by prolonged exposure to respirable coal dust (CD), with limited therapeutic options. Here, we explored the antifibrotic effects of metformin (Met) in CD-nanoparticle (CD-NP)-induced PF, focusing on its preventive and therapeutic potential. In vivo, Met was administered at different doses (low: 31.
View Article and Find Full Text PDF