Communication between alveolar macrophages and fibroblasts via the TNFSF12-TNFRSF12A pathway promotes pulmonary fibrosis in severe COVID-19 patients.
Humans
COVID-19
/ complications
Macrophages, Alveolar
/ metabolism
Fibroblasts
/ metabolism
Pulmonary Fibrosis
/ pathology
Signal Transduction
TWEAK Receptor
/ metabolism
Cytokine TWEAK
/ metabolism
Cell Communication
Male
SARS-CoV-2
Female
Middle Aged
Cell Proliferation
Lung
/ pathology
Severity of Illness Index
Alveolar macrophages
Cell communication
Fibroblasts
Pulmonary fibrosis
Severe COVID-19
TNFSF12-TNFRSF12A pathway
Therapeutic strategy
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
29 Jul 2024
29 Jul 2024
Historique:
received:
30
10
2023
accepted:
05
01
2024
medline:
30
7
2024
pubmed:
30
7
2024
entrez:
29
7
2024
Statut:
epublish
Résumé
Severe COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial. In this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients. We conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal. Our analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages. The TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease.
Sections du résumé
BACKGROUND
BACKGROUND
Severe COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial.
OBJECTIVE
OBJECTIVE
In this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients.
METHODS
METHODS
We conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal.
RESULTS
RESULTS
Our analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages.
CONCLUSION
CONCLUSIONS
The TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease.
Identifiants
pubmed: 39075394
doi: 10.1186/s12967-024-05381-7
pii: 10.1186/s12967-024-05381-7
doi:
Substances chimiques
TWEAK Receptor
0
Cytokine TWEAK
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
698Informations de copyright
© 2024. The Author(s).
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