Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis
Abstract Pulmonary fibrosis (PF) is a life-threatening condition characterised by excessive extracellular matrix deposition and tissue scarring. While much of PF research has focused on alveolar epithelial cells and fibroblasts, endothelial cells have emerged as active contributors to the disease in...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-07-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07824-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849341649399840768 |
|---|---|
| author | Lena Möbus Laura Ylä-Outinen Luca Mannino Giorgia Migliaccio Karoliina Kosunen Nicoletta D’Alessandro Angela Serra Dario Greco |
| author_facet | Lena Möbus Laura Ylä-Outinen Luca Mannino Giorgia Migliaccio Karoliina Kosunen Nicoletta D’Alessandro Angela Serra Dario Greco |
| author_sort | Lena Möbus |
| collection | DOAJ |
| description | Abstract Pulmonary fibrosis (PF) is a life-threatening condition characterised by excessive extracellular matrix deposition and tissue scarring. While much of PF research has focused on alveolar epithelial cells and fibroblasts, endothelial cells have emerged as active contributors to the disease initiation, especially in the context of systemic exposure to pro-fibrotic substances. Here, we investigate early transcriptomic and secretory responses of human umbilical vein endothelial cells (HUVEC) to subtoxic doses of bleomycin, a known pro-fibrotic agent, and TGF-beta, a key cytokine in fibrosis. Bleomycin exposure induced a rapid and extensive shift in the endothelial transcriptional programme, including signatures of endothelial to mesenchymal transition, cellular senescence, and immune cell recruitment. These findings suggest endothelial cells as early initiators of pro-fibrotic signals, independent of contributions from other cell types. In contrast, TGF-beta effects were limited and transient, indicating its pro-fibrotic action may require another initial stimulus and interplay with other cells like fibroblasts. This study highlights the sensitivity of endothelial cells to pro-fibrotic exposure and provides a blueprint of early pro-fibrotic mechanisms that may operate on organs such as the lungs systemically via the endothelium, emphasising its pivotal role in PF pathogenesis. |
| format | Article |
| id | doaj-art-7908484a507341af90fbd6da66baf39e |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-7908484a507341af90fbd6da66baf39e2025-08-20T03:43:34ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111210.1038/s41419-025-07824-5Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosisLena Möbus0Laura Ylä-Outinen1Luca Mannino2Giorgia Migliaccio3Karoliina Kosunen4Nicoletta D’Alessandro5Angela Serra6Dario Greco7Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Faculty of Medicine and Health Technology, Tampere UniversityAbstract Pulmonary fibrosis (PF) is a life-threatening condition characterised by excessive extracellular matrix deposition and tissue scarring. While much of PF research has focused on alveolar epithelial cells and fibroblasts, endothelial cells have emerged as active contributors to the disease initiation, especially in the context of systemic exposure to pro-fibrotic substances. Here, we investigate early transcriptomic and secretory responses of human umbilical vein endothelial cells (HUVEC) to subtoxic doses of bleomycin, a known pro-fibrotic agent, and TGF-beta, a key cytokine in fibrosis. Bleomycin exposure induced a rapid and extensive shift in the endothelial transcriptional programme, including signatures of endothelial to mesenchymal transition, cellular senescence, and immune cell recruitment. These findings suggest endothelial cells as early initiators of pro-fibrotic signals, independent of contributions from other cell types. In contrast, TGF-beta effects were limited and transient, indicating its pro-fibrotic action may require another initial stimulus and interplay with other cells like fibroblasts. This study highlights the sensitivity of endothelial cells to pro-fibrotic exposure and provides a blueprint of early pro-fibrotic mechanisms that may operate on organs such as the lungs systemically via the endothelium, emphasising its pivotal role in PF pathogenesis.https://doi.org/10.1038/s41419-025-07824-5 |
| spellingShingle | Lena Möbus Laura Ylä-Outinen Luca Mannino Giorgia Migliaccio Karoliina Kosunen Nicoletta D’Alessandro Angela Serra Dario Greco Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis Cell Death and Disease |
| title | Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis |
| title_full | Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis |
| title_fullStr | Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis |
| title_full_unstemmed | Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis |
| title_short | Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis |
| title_sort | endothelial sensitivity to pro fibrotic signals links systemic exposure to pulmonary fibrosis |
| url | https://doi.org/10.1038/s41419-025-07824-5 |
| work_keys_str_mv | AT lenamobus endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT lauraylaoutinen endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT lucamannino endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT giorgiamigliaccio endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT karoliinakosunen endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT nicolettadalessandro endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT angelaserra endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis AT dariogreco endothelialsensitivitytoprofibroticsignalslinkssystemicexposuretopulmonaryfibrosis |