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TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals
Lymphatic systems play important roles in the maintenance of fluid homeostasis and undergo anatomical and physiological changes during inflammation and aging. While lymphatic endothelial cells (LECs) undergo mesenchymal transition in response to transforming growth factor-β (TGF-β), the molecular me...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194440/ https://www.ncbi.nlm.nih.gov/pubmed/32357159 http://dx.doi.org/10.1371/journal.pone.0232356 |
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author | Yoshimatsu, Yasuhiro Kimuro, Shiori Pauty, Joris Takagaki, Kazuki Nomiyama, Sanae Inagawa, Akihiko Maeda, Kentaro Podyma-Inoue, Katarzyna A. Kajiya, Kentaro Matsunaga, Yukiko T. Watabe, Tetsuro |
author_facet | Yoshimatsu, Yasuhiro Kimuro, Shiori Pauty, Joris Takagaki, Kazuki Nomiyama, Sanae Inagawa, Akihiko Maeda, Kentaro Podyma-Inoue, Katarzyna A. Kajiya, Kentaro Matsunaga, Yukiko T. Watabe, Tetsuro |
author_sort | Yoshimatsu, Yasuhiro |
collection | PubMed |
description | Lymphatic systems play important roles in the maintenance of fluid homeostasis and undergo anatomical and physiological changes during inflammation and aging. While lymphatic endothelial cells (LECs) undergo mesenchymal transition in response to transforming growth factor-β (TGF-β), the molecular mechanisms underlying endothelial-to-mesenchymal transition (EndMT) of LECs remain largely unknown. In this study, we examined the effect of TGF-β2 and tumor necrosis factor-α (TNF-α), an inflammatory cytokine, on EndMT using human skin-derived lymphatic endothelial cells (HDLECs). TGF-β2-treated HDLECs showed increased expression of SM22α, a mesenchymal cell marker accompanied by increased cell motility and vascular permeability, suggesting HDLECs to undergo EndMT. Our data also revealed that TNF-α could enhance TGF-β2-induced EndMT of HDLECs. Furthermore, both cytokines induced the production of Activin A while decreasing the expression of its inhibitory molecule Follistatin, and thus enhancing EndMT. Finally, we demonstrated that human dermal lymphatic vessels underwent EndMT during aging, characterized by double immunostaining for LYVE1 and SM22α. These results suggest that both TGF-β and TNF-α signals play a central role in EndMT of LECs and could be potential targets for senile edema. |
format | Online Article Text |
id | pubmed-7194440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71944402020-05-12 TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals Yoshimatsu, Yasuhiro Kimuro, Shiori Pauty, Joris Takagaki, Kazuki Nomiyama, Sanae Inagawa, Akihiko Maeda, Kentaro Podyma-Inoue, Katarzyna A. Kajiya, Kentaro Matsunaga, Yukiko T. Watabe, Tetsuro PLoS One Research Article Lymphatic systems play important roles in the maintenance of fluid homeostasis and undergo anatomical and physiological changes during inflammation and aging. While lymphatic endothelial cells (LECs) undergo mesenchymal transition in response to transforming growth factor-β (TGF-β), the molecular mechanisms underlying endothelial-to-mesenchymal transition (EndMT) of LECs remain largely unknown. In this study, we examined the effect of TGF-β2 and tumor necrosis factor-α (TNF-α), an inflammatory cytokine, on EndMT using human skin-derived lymphatic endothelial cells (HDLECs). TGF-β2-treated HDLECs showed increased expression of SM22α, a mesenchymal cell marker accompanied by increased cell motility and vascular permeability, suggesting HDLECs to undergo EndMT. Our data also revealed that TNF-α could enhance TGF-β2-induced EndMT of HDLECs. Furthermore, both cytokines induced the production of Activin A while decreasing the expression of its inhibitory molecule Follistatin, and thus enhancing EndMT. Finally, we demonstrated that human dermal lymphatic vessels underwent EndMT during aging, characterized by double immunostaining for LYVE1 and SM22α. These results suggest that both TGF-β and TNF-α signals play a central role in EndMT of LECs and could be potential targets for senile edema. Public Library of Science 2020-05-01 /pmc/articles/PMC7194440/ /pubmed/32357159 http://dx.doi.org/10.1371/journal.pone.0232356 Text en © 2020 Yoshimatsu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yoshimatsu, Yasuhiro Kimuro, Shiori Pauty, Joris Takagaki, Kazuki Nomiyama, Sanae Inagawa, Akihiko Maeda, Kentaro Podyma-Inoue, Katarzyna A. Kajiya, Kentaro Matsunaga, Yukiko T. Watabe, Tetsuro TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals |
title | TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals |
title_full | TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals |
title_fullStr | TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals |
title_full_unstemmed | TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals |
title_short | TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals |
title_sort | tgf-beta and tnf-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of activin signals |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194440/ https://www.ncbi.nlm.nih.gov/pubmed/32357159 http://dx.doi.org/10.1371/journal.pone.0232356 |
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