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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Main Authors: Fan Lu, Wang Huixia, Xu Nuo, Guo Yun, Li Ling
Format: Article
Language:English
Published: University of Belgrade, University of Novi Sad 2024-01-01
Series:Archives of Biological Sciences
Subjects:
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.
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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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