Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice
Abstract The current study evaluated the role of Hey2 transcription factor in radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbi...
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Nature Portfolio
2017
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oai:doaj.org-article:16e3d124e47b4cf3a626bb2025127e362021-12-02T16:06:22ZEndothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice10.1038/s41598-017-05389-82045-2322https://doaj.org/article/16e3d124e47b4cf3a626bb2025127e362017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05389-8https://doaj.org/toc/2045-2322Abstract The current study evaluated the role of Hey2 transcription factor in radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irradiation and radiation proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in radiation proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage.Elodie MintetJérémy LavigneVincent PagetGeorges TarletValérie BuardOlivier GuipaudJean-Christophe SabourinMaria-Luisa Iruela-ArispeFabien MilliatAgnès FrançoisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) |
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Medicine R Science Q Elodie Mintet Jérémy Lavigne Vincent Paget Georges Tarlet Valérie Buard Olivier Guipaud Jean-Christophe Sabourin Maria-Luisa Iruela-Arispe Fabien Milliat Agnès François Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| description |
Abstract The current study evaluated the role of Hey2 transcription factor in radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irradiation and radiation proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in radiation proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage. |
| format |
article |
| author |
Elodie Mintet Jérémy Lavigne Vincent Paget Georges Tarlet Valérie Buard Olivier Guipaud Jean-Christophe Sabourin Maria-Luisa Iruela-Arispe Fabien Milliat Agnès François |
| author_facet |
Elodie Mintet Jérémy Lavigne Vincent Paget Georges Tarlet Valérie Buard Olivier Guipaud Jean-Christophe Sabourin Maria-Luisa Iruela-Arispe Fabien Milliat Agnès François |
| author_sort |
Elodie Mintet |
| title |
Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| title_short |
Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| title_full |
Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| title_fullStr |
Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| title_full_unstemmed |
Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| title_sort |
endothelial hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/16e3d124e47b4cf3a626bb2025127e36 |
| work_keys_str_mv |
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1718385008015572992 |