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Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation and abnormal accumulation of extracellular matrix in the lungs. After lung injury, M2 macrophages mediate the pathogenesis of pulmonary fibrosis by secreting fibrotic cytokines that promote myof...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10215911/ https://www.ncbi.nlm.nih.gov/pubmed/37238950 http://dx.doi.org/10.3390/biomedicines11051279 |
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author | Zhang, Yunna Fu, Jiafeng Han, Yang Feng, Dandan Yue, Shaojie Zhou, Yan Luo, Ziqiang |
author_facet | Zhang, Yunna Fu, Jiafeng Han, Yang Feng, Dandan Yue, Shaojie Zhou, Yan Luo, Ziqiang |
author_sort | Zhang, Yunna |
collection | PubMed |
description | Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation and abnormal accumulation of extracellular matrix in the lungs. After lung injury, M2 macrophages mediate the pathogenesis of pulmonary fibrosis by secreting fibrotic cytokines that promote myofibroblast activation. The TWIK-related potassium channel (TREK–1, also known as KCNK2) is a K2P channel that is highly expressed in cardiac, lung, and other tissues; it worsens various tumors, such as ovarian cancer and prostate cancer, and mediates cardiac fibrosis. However, the role of TREK–1 in lung fibrosis remains unclear. This study aimed to examine the effects of TREK–1 on bleomycin (BLM)-induced lung fibrosis. The results show that TREK–1 knockdown, mediated by the adenovirus or pharmacological inhibition of TREK–1 with fluoxetine, resulted in diminished BLM-induced lung fibrosis. TREK–1 overexpression in macrophages remarkably increased the M2 phenotype, resulting in fibroblast activation. Furthermore, TREK–1 knockdown and fluoxetine administration directly reduced the differentiation of fibroblasts to myofibroblasts by inhibiting the focal adhesion kinase (FAK)/p38 mitogen-activated protein kinases (p38)/Yes-associated protein (YAP) signaling pathway. In conclusion, TREK–1 plays a central role in the pathogenesis of BLM-induced lung fibrosis, which serves as a theoretical basis for the inhibition of TREK–1 as a potential therapy protocol for lung fibrosis. |
format | Online Article Text |
id | pubmed-10215911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102159112023-05-27 Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation Zhang, Yunna Fu, Jiafeng Han, Yang Feng, Dandan Yue, Shaojie Zhou, Yan Luo, Ziqiang Biomedicines Article Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation and abnormal accumulation of extracellular matrix in the lungs. After lung injury, M2 macrophages mediate the pathogenesis of pulmonary fibrosis by secreting fibrotic cytokines that promote myofibroblast activation. The TWIK-related potassium channel (TREK–1, also known as KCNK2) is a K2P channel that is highly expressed in cardiac, lung, and other tissues; it worsens various tumors, such as ovarian cancer and prostate cancer, and mediates cardiac fibrosis. However, the role of TREK–1 in lung fibrosis remains unclear. This study aimed to examine the effects of TREK–1 on bleomycin (BLM)-induced lung fibrosis. The results show that TREK–1 knockdown, mediated by the adenovirus or pharmacological inhibition of TREK–1 with fluoxetine, resulted in diminished BLM-induced lung fibrosis. TREK–1 overexpression in macrophages remarkably increased the M2 phenotype, resulting in fibroblast activation. Furthermore, TREK–1 knockdown and fluoxetine administration directly reduced the differentiation of fibroblasts to myofibroblasts by inhibiting the focal adhesion kinase (FAK)/p38 mitogen-activated protein kinases (p38)/Yes-associated protein (YAP) signaling pathway. In conclusion, TREK–1 plays a central role in the pathogenesis of BLM-induced lung fibrosis, which serves as a theoretical basis for the inhibition of TREK–1 as a potential therapy protocol for lung fibrosis. MDPI 2023-04-26 /pmc/articles/PMC10215911/ /pubmed/37238950 http://dx.doi.org/10.3390/biomedicines11051279 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Yunna Fu, Jiafeng Han, Yang Feng, Dandan Yue, Shaojie Zhou, Yan Luo, Ziqiang Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation |
title | Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation |
title_full | Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation |
title_fullStr | Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation |
title_full_unstemmed | Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation |
title_short | Two-Pore-Domain Potassium Channel TREK–1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation |
title_sort | two-pore-domain potassium channel trek–1 mediates pulmonary fibrosis through macrophage m2 polarization and by direct promotion of fibroblast differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10215911/ https://www.ncbi.nlm.nih.gov/pubmed/37238950 http://dx.doi.org/10.3390/biomedicines11051279 |
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