Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect

Exposure to fine particulate matter (PM2.5) and heavy metals (HMs) in the air is closely associated with the incidence and exacerbation of pulmonary fibrosis. Although the specific responses of alveolar epithelial cells (AECs) and lung fibroblasts to PM2.5 or HM exposure have been well defined, the...

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Main Authors: Jung-Yun Choi, Minje Kang, Ji-Hye Jung, Woo Jin Kim, Hyo-Seon Yang, Kyuhong Lee, Jooyeon Lee, Se-Ran Yang, Chin Kook Rhee, Seok-Ho Hong
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324014775
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author Jung-Yun Choi
Minje Kang
Ji-Hye Jung
Woo Jin Kim
Hyo-Seon Yang
Kyuhong Lee
Jooyeon Lee
Se-Ran Yang
Chin Kook Rhee
Seok-Ho Hong
author_facet Jung-Yun Choi
Minje Kang
Ji-Hye Jung
Woo Jin Kim
Hyo-Seon Yang
Kyuhong Lee
Jooyeon Lee
Se-Ran Yang
Chin Kook Rhee
Seok-Ho Hong
author_sort Jung-Yun Choi
collection DOAJ
description Exposure to fine particulate matter (PM2.5) and heavy metals (HMs) in the air is closely associated with the incidence and exacerbation of pulmonary fibrosis. Although the specific responses of alveolar epithelial cells (AECs) and lung fibroblasts to PM2.5 or HM exposure have been well defined, the cellular responses of lung fibroblasts to PM2.5 or HM exposure and the subsequent interactions with AECs remain poorly investigated. In this study, we demonstrated that human lung fibroblasts exposed to PM2.5 or lead (Pb) induced fibrotic changes and apoptosis in AECs. Lung fibroblasts exposed to PM2.5 induced fibrotic changes in AECs via a paracrine action. We further evaluated the detrimental effects of four HMs (cadmium, lead, arsenic, and manganese) present at the highest levels in the ambient air of South Korea, and investigated their paracrine effects on AECs. We found that long-term (14 passages) exposure to these HMs negatively affected the growth, migration, and survival of lung fibroblasts. Notably, manganese (Mn) significantly upregulated the expression of fibrotic markers with the activation of extracellular signal-regulated kinase (ERK) signaling in lung fibroblasts. However, treatment with conditioned medium (CM) collected from Mn-treated lung fibroblasts did not induce fibrotic changes in AECs. Interestingly, CM from Pb-treated lung fibroblasts significantly upregulated markers for fibrosis and apoptosis in AECs via activation of the ERK signaling pathway. These results suggest that understanding interactions between fibroblasts and AECs may provide useful strategies against PM or HM-induced injuries in alveolar tissue.
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spelling doaj-art-61ac41fc4da54f45be628932777f97c82025-08-20T02:21:04ZengElsevierEcotoxicology and Environmental Safety0147-65132024-12-0128811740110.1016/j.ecoenv.2024.117401Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effectJung-Yun Choi0Minje Kang1Ji-Hye Jung2Woo Jin Kim3Hyo-Seon Yang4Kyuhong Lee5Jooyeon Lee6Se-Ran Yang7Chin Kook Rhee8Seok-Ho Hong9Department of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea; Department of Integrated Particulate Matter Management, Kangwon National University, Chuncheon, Republic of KoreaRespiratory Safety Research Center, Korea Institute of Toxicology, Jeongeup, Republic of KoreaRespiratory Safety Research Center, Korea Institute of Toxicology, Jeongeup, Republic of Korea; Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea; Department of Integrated Particulate Matter Management, Kangwon National University, Chuncheon, Republic of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Republic of KoreaDepartment of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea; Department of Integrated Particulate Matter Management, Kangwon National University, Chuncheon, Republic of Korea; KW-Bio Co. Ltd., Chuncheon, Republic of Korea; Correspondence to: Department of Internal Medicine, School of Medicine, Kangwon National University, Kangwondaehakgil-1, Chuncheon, Gangwon-do 24341, Republic of Korea.Exposure to fine particulate matter (PM2.5) and heavy metals (HMs) in the air is closely associated with the incidence and exacerbation of pulmonary fibrosis. Although the specific responses of alveolar epithelial cells (AECs) and lung fibroblasts to PM2.5 or HM exposure have been well defined, the cellular responses of lung fibroblasts to PM2.5 or HM exposure and the subsequent interactions with AECs remain poorly investigated. In this study, we demonstrated that human lung fibroblasts exposed to PM2.5 or lead (Pb) induced fibrotic changes and apoptosis in AECs. Lung fibroblasts exposed to PM2.5 induced fibrotic changes in AECs via a paracrine action. We further evaluated the detrimental effects of four HMs (cadmium, lead, arsenic, and manganese) present at the highest levels in the ambient air of South Korea, and investigated their paracrine effects on AECs. We found that long-term (14 passages) exposure to these HMs negatively affected the growth, migration, and survival of lung fibroblasts. Notably, manganese (Mn) significantly upregulated the expression of fibrotic markers with the activation of extracellular signal-regulated kinase (ERK) signaling in lung fibroblasts. However, treatment with conditioned medium (CM) collected from Mn-treated lung fibroblasts did not induce fibrotic changes in AECs. Interestingly, CM from Pb-treated lung fibroblasts significantly upregulated markers for fibrosis and apoptosis in AECs via activation of the ERK signaling pathway. These results suggest that understanding interactions between fibroblasts and AECs may provide useful strategies against PM or HM-induced injuries in alveolar tissue.http://www.sciencedirect.com/science/article/pii/S0147651324014775Particulate matterLeadFibrosisApoptosisLung fibroblastsAlveolar epithelial cells
spellingShingle Jung-Yun Choi
Minje Kang
Ji-Hye Jung
Woo Jin Kim
Hyo-Seon Yang
Kyuhong Lee
Jooyeon Lee
Se-Ran Yang
Chin Kook Rhee
Seok-Ho Hong
Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
Ecotoxicology and Environmental Safety
Particulate matter
Lead
Fibrosis
Apoptosis
Lung fibroblasts
Alveolar epithelial cells
title Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
title_full Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
title_fullStr Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
title_full_unstemmed Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
title_short Exposure of lung fibroblasts to PM2.5 and lead (Pb) induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
title_sort exposure of lung fibroblasts to pm2 5 and lead pb induces fibrosis and apoptosis in alveolar epithelial cells via a paracrine effect
topic Particulate matter
Lead
Fibrosis
Apoptosis
Lung fibroblasts
Alveolar epithelial cells
url http://www.sciencedirect.com/science/article/pii/S0147651324014775
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