Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia
Mycoplasma pneumoniae (MP), one of the smallest prokaryotic microorganisms capable of independent survival, causes respiratory tract infections and various extrapulmonary diseases. Mycoplasma pneumoniae pneumonia (MPP) is the most significant clinical manifestation, often leading to complications su...
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University of Belgrade, University of Novi Sad
2024-01-01
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Series: | Archives of Biological Sciences |
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Online Access: | https://doiserbia.nb.rs/img/doi/0354-4664/2024/0354-46642400033F.pdf |
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author | Fan Lu Wang Huixia Xu Nuo Guo Yun Li Ling |
author_facet | Fan Lu Wang Huixia Xu Nuo Guo Yun Li Ling |
author_sort | Fan Lu |
collection | DOAJ |
description | Mycoplasma pneumoniae (MP), one of the smallest prokaryotic microorganisms capable of independent survival, causes respiratory tract infections and various extrapulmonary diseases. Mycoplasma pneumoniae pneumonia (MPP) is the most significant clinical manifestation, often leading to complications such as atelectasis and pulmonary fibrosis. We explored the role of the pulmonary microenvironment in regulating epithelial-mesenchymal transition (EMT) in MPP patients with atelectasis. Transcriptome sequencing revealed significant upregulation of pathways including transforming growth factor beta (TGF-β), tumor protein 53 (P53), protein kinase Hippo, Ras-proximate-1 or Ras-related protein 1 (Rap1), and members of class O forkhead box proteins (FoxO) in cells exposed to bronchoalveolar lavage fluid (BALF) from MPP patients with atelectasis. Among these, the TGF-β pathway exhibited the most pronounced changes in gene expression. Further analysis confirmed that BALF from these patients induced EMT in human bronchial epithelial cells and mouse lung tissues and that TGF-β receptor kinase inhibitor (TRKI) effectively reversed this process. In conclusion, the pulmonary microenvironment in MPP patients with atelectasis promotes EMT in the lungs, with TGF-β playing a key role in this process. This may represent a crucial mechanism contributing to pulmonary fibrosis, underscoring the need to focus on the pulmonary microenvironment and TGF-β-targeted therapies for the prevention and management of pulmonary fibrosis in these patients. |
format | Article |
id | doaj-art-6728ac3bc7ed4d92a43a14ca77dc81ed |
institution | Kabale University |
issn | 0354-4664 1821-4339 |
language | English |
publishDate | 2024-01-01 |
publisher | University of Belgrade, University of Novi Sad |
record_format | Article |
series | Archives of Biological Sciences |
spelling | doaj-art-6728ac3bc7ed4d92a43a14ca77dc81ed2025-01-30T06:38:39ZengUniversity of Belgrade, University of Novi SadArchives of Biological Sciences0354-46641821-43392024-01-0176443144410.2298/ABS240720033F0354-46642400033FInvolvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumoniaFan Lu0https://orcid.org/0009-0003-1916-1672Wang Huixia1Xu Nuo2https://orcid.org/0009-0004-3370-3279Guo Yun3https://orcid.org/0000-0002-8107-0507Li Ling4https://orcid.org/0000-0001-7487-135XDepartment of Respiratory Medicine and Clinical Allergy Center, The Affiliated Children´s Hospital of Jiangnan University, Wuxi, ChinaDepartment of Pediatric Respiratory Medicine, Pediatric Respiratory Medicine of Zhumadian Central Hospital, Zhumadian, ChinaDepartment of Respiratory Medicine and Clinical Allergy Center, The Affiliated Wuxi Peoples´ Hospital of Nanjing Medical University, Wuxi Children´s Hospital, Wuxi, ChinaDepartment of Respiratory Medicine and Clinical Allergy Center, The Affiliated Children´s Hospital of Jiangnan University, Wuxi, China + Department of Respiratory Medicine and Clinical Allergy Center, The Affiliated Wuxi Peoples´ Hospital of Nanjing Medical University, Wuxi Children´s Hospital, Wuxi, ChinaDepartment of Respiratory Medicine and Clinical Allergy Center, The Affiliated Children´s Hospital of Jiangnan University, Wuxi, China + Department of Respiratory Medicine and Clinical Allergy Center, The Affiliated Wuxi Peoples´ Hospital of Nanjing Medical University, Wuxi Children´s Hospital, Wuxi, ChinaMycoplasma pneumoniae (MP), one of the smallest prokaryotic microorganisms capable of independent survival, causes respiratory tract infections and various extrapulmonary diseases. Mycoplasma pneumoniae pneumonia (MPP) is the most significant clinical manifestation, often leading to complications such as atelectasis and pulmonary fibrosis. We explored the role of the pulmonary microenvironment in regulating epithelial-mesenchymal transition (EMT) in MPP patients with atelectasis. Transcriptome sequencing revealed significant upregulation of pathways including transforming growth factor beta (TGF-β), tumor protein 53 (P53), protein kinase Hippo, Ras-proximate-1 or Ras-related protein 1 (Rap1), and members of class O forkhead box proteins (FoxO) in cells exposed to bronchoalveolar lavage fluid (BALF) from MPP patients with atelectasis. Among these, the TGF-β pathway exhibited the most pronounced changes in gene expression. Further analysis confirmed that BALF from these patients induced EMT in human bronchial epithelial cells and mouse lung tissues and that TGF-β receptor kinase inhibitor (TRKI) effectively reversed this process. In conclusion, the pulmonary microenvironment in MPP patients with atelectasis promotes EMT in the lungs, with TGF-β playing a key role in this process. This may represent a crucial mechanism contributing to pulmonary fibrosis, underscoring the need to focus on the pulmonary microenvironment and TGF-β-targeted therapies for the prevention and management of pulmonary fibrosis in these patients.https://doiserbia.nb.rs/img/doi/0354-4664/2024/0354-46642400033F.pdfmycoplasma pneumoniae pneumonia (mpp)atelectasismicroenvironmentepithelial mesenchymaltransition (emt)tgf-β |
spellingShingle | Fan Lu Wang Huixia Xu Nuo Guo Yun Li Ling Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia Archives of Biological Sciences mycoplasma pneumoniae pneumonia (mpp) atelectasis microenvironment epithelial mesenchymaltransition (emt) tgf-β |
title | Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia |
title_full | Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia |
title_fullStr | Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia |
title_full_unstemmed | Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia |
title_short | Involvement of the TGF-β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in Mycoplasma pneumoniae pneumonia |
title_sort | involvement of the tgf β pathway in epithelialmesenchymal transition promoted by the pulmonary microenvironment in mycoplasma pneumoniae pneumonia |
topic | mycoplasma pneumoniae pneumonia (mpp) atelectasis microenvironment epithelial mesenchymaltransition (emt) tgf-β |
url | https://doiserbia.nb.rs/img/doi/0354-4664/2024/0354-46642400033F.pdf |
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