Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection
Pulmonary fibrosis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of death in patients with COVID-19. β-catenin, a key molecule in the Wnt/β-catenin signaling pathway, has been shown to be involved in the development of pulmonary fibrosis (e.g., id...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/6/394 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849343018127065088 |
|---|---|
| author | Min Jiang Jiaqi Hou Qianqian Chai Shihao Yin Qian Liu |
| author_facet | Min Jiang Jiaqi Hou Qianqian Chai Shihao Yin Qian Liu |
| author_sort | Min Jiang |
| collection | DOAJ |
| description | Pulmonary fibrosis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of death in patients with COVID-19. β-catenin, a key molecule in the Wnt/β-catenin signaling pathway, has been shown to be involved in the development of pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis, silicosis). In this study, we developed a SARS-CoV-2-infected A549-hACE2 cell model to evaluate the efficacy of the A549-hACE2 monoclonal cell line against SARS-CoV-2 infection. The A549-hACE2 cells were then subjected to either knockdown or overexpression of the effector β-catenin, and the modified cells were subsequently infected with SARS-CoV-2. Additionally, we employed transcriptomics and raw letter analysis approaches to investigate other potential effects of β-catenin on SARS-CoV-2 infection. We successfully established a model of cellular fibrosis induced by SARS-CoV-2 infection in lung-derived cells. This model can be utilized to investigate the molecular biological mechanisms and cellular signaling pathways associated with virus-induced lung fibrosis. The results of our mechanistic studies indicate that β-catenin plays a significant role in lung fibrosis resulting from SARS-CoV-2 infection. Furthermore, the inhibition of β-catenin mitigated the accumulation of mesenchymal stroma in A549-hACE2 cells. Additionally, β-catenin knockdown was found to facilitate multi-pathway crosstalk following SARS-CoV-2 infection. The fact that β-catenin overexpression did not exacerbate cellular fibrosis may be attributed to the activation of PPP2R2B. |
| format | Article |
| id | doaj-art-8f655abdcb274d4aba0d0c409f117f75 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-8f655abdcb274d4aba0d0c409f117f752025-08-20T03:43:11ZengMDPI AGCells2073-44092025-03-0114639410.3390/cells14060394Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 InfectionMin Jiang0Jiaqi Hou1Qianqian Chai2Shihao Yin3Qian Liu4Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, ChinaDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, ChinaDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, ChinaDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, ChinaDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, ChinaPulmonary fibrosis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of death in patients with COVID-19. β-catenin, a key molecule in the Wnt/β-catenin signaling pathway, has been shown to be involved in the development of pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis, silicosis). In this study, we developed a SARS-CoV-2-infected A549-hACE2 cell model to evaluate the efficacy of the A549-hACE2 monoclonal cell line against SARS-CoV-2 infection. The A549-hACE2 cells were then subjected to either knockdown or overexpression of the effector β-catenin, and the modified cells were subsequently infected with SARS-CoV-2. Additionally, we employed transcriptomics and raw letter analysis approaches to investigate other potential effects of β-catenin on SARS-CoV-2 infection. We successfully established a model of cellular fibrosis induced by SARS-CoV-2 infection in lung-derived cells. This model can be utilized to investigate the molecular biological mechanisms and cellular signaling pathways associated with virus-induced lung fibrosis. The results of our mechanistic studies indicate that β-catenin plays a significant role in lung fibrosis resulting from SARS-CoV-2 infection. Furthermore, the inhibition of β-catenin mitigated the accumulation of mesenchymal stroma in A549-hACE2 cells. Additionally, β-catenin knockdown was found to facilitate multi-pathway crosstalk following SARS-CoV-2 infection. The fact that β-catenin overexpression did not exacerbate cellular fibrosis may be attributed to the activation of PPP2R2B.https://www.mdpi.com/2073-4409/14/6/394β-cateninpulmonary fibrosisSARS-CoV-2transcriptomicsWNT signaling |
| spellingShingle | Min Jiang Jiaqi Hou Qianqian Chai Shihao Yin Qian Liu Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection Cells β-catenin pulmonary fibrosis SARS-CoV-2 transcriptomics WNT signaling |
| title | Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection |
| title_full | Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection |
| title_fullStr | Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection |
| title_full_unstemmed | Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection |
| title_short | Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection |
| title_sort | mechanism of β catenin in pulmonary fibrosis following sars cov 2 infection |
| topic | β-catenin pulmonary fibrosis SARS-CoV-2 transcriptomics WNT signaling |
| url | https://www.mdpi.com/2073-4409/14/6/394 |
| work_keys_str_mv | AT minjiang mechanismofbcatenininpulmonaryfibrosisfollowingsarscov2infection AT jiaqihou mechanismofbcatenininpulmonaryfibrosisfollowingsarscov2infection AT qianqianchai mechanismofbcatenininpulmonaryfibrosisfollowingsarscov2infection AT shihaoyin mechanismofbcatenininpulmonaryfibrosisfollowingsarscov2infection AT qianliu mechanismofbcatenininpulmonaryfibrosisfollowingsarscov2infection |