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Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid artery ligation

View ORCID ProfileYoshito Yamashiro, Karina Ramirez, Kazuaki Nagayama, Shuhei Tomita, Yoshiaki Kubota, View ORCID ProfileHiromi Yanagisawa
doi: https://doi.org/10.1101/2021.08.13.456319
Yoshito Yamashiro
1Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki 305-8577, Japan
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  • ORCID record for Yoshito Yamashiro
  • For correspondence: yamayoshito@tara.tsukuba.ac.jp hkyanagisawa@tara.tsukuba.ac.jp
Karina Ramirez
1Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki 305-8577, Japan
2Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Ibaraki, 305-8577, Japan
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Kazuaki Nagayama
3Graduate School of Mechanical Systems Engineering, Ibaraki University, Ibaraki, 316-8511, Japan
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Shuhei Tomita
4Department of Pharmacology, Osaka City University Graduate School of Medicine, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
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Yoshiaki Kubota
5Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Hiromi Yanagisawa
1Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki 305-8577, Japan
6Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, Japan
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  • For correspondence: yamayoshito@tara.tsukuba.ac.jp hkyanagisawa@tara.tsukuba.ac.jp
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Abstract

Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodeling. Carotid artery ligation is commonly used for induction of neointima formation and vessel stenosis; however, the precise regulatory mechanism of vascular remodeling is not entirely understood. In this study, we showed that resident endothelial cells (ECs) are the origin of neointima cells and ECs transiently expressed CD45 in the early stage of neointima formation accompanied by increased expression of EndMT markers. In vitro, CD45-positive EndMT was induced by stabilization of HIF-1α with cobalt chloride or VHL inhibitor in human primary ECs, which mimicked the hypoxic condition of ligated artery, and promoted the formation of integrin α11-SHARPIN complex. Notably, a CD45 phosphatase inhibitor disrupted this complex, thereby destabilizing cell-cell junctions. These results suggest that the CD45 activity is required for the retention of an EC phenotype and cell-cell junctions during EndMT (termed “partial EndMT”). We thus propose a novel mechanism of partial EndMT that contributes to lumen re-organization during vascular injury.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 14, 2021.
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Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid artery ligation
Yoshito Yamashiro, Karina Ramirez, Kazuaki Nagayama, Shuhei Tomita, Yoshiaki Kubota, Hiromi Yanagisawa
bioRxiv 2021.08.13.456319; doi: https://doi.org/10.1101/2021.08.13.456319
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Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid artery ligation
Yoshito Yamashiro, Karina Ramirez, Kazuaki Nagayama, Shuhei Tomita, Yoshiaki Kubota, Hiromi Yanagisawa
bioRxiv 2021.08.13.456319; doi: https://doi.org/10.1101/2021.08.13.456319

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