High Glucose Activates YAP Signaling to Promote Vascular Inflammation
Autor: | Bruno Poirier, Christine Girardot, Elise F. Villard, Bertrand Léger, Jeremy Ortillon, Etienne Guillot, Laetitia Ledein, Sandra Beeské, Jean-Christophe Le Bail, Philip Janiak, Véronique Blanchard, Patrice Brieu, Souâd Naimi, Marco Meloni |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
vascular complications Physiology Regulator Inflammation Endothelial activation 03 medical and health sciences 0302 clinical medicine In vivo Diabetes mellitus Physiology (medical) medicine QP1-981 YAP/TAZ Original Research diabetes Vascular inflammation Chemistry Monocyte medicine.disease In vitro endothelial cells Cell biology 030104 developmental biology medicine.anatomical_structure inflammation 030220 oncology & carcinogenesis medicine.symptom |
Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 12 (2021) |
ISSN: | 1664-042X |
DOI: | 10.3389/fphys.2021.665994 |
Popis: | Background and AimsThe YAP/TAZ signaling is known to regulate endothelial activation and vascular inflammation in response to shear stress. Moreover, YAP/TAZ signaling plays a role in the progression of cancers and renal damage associated with diabetes. However, whether YAP/TAZ signaling is also implicated in diabetes-associated vascular complications is not known.MethodsThe effect of high glucose on YAP/TAZ signaling was firstly evaluated in vitro on endothelial cells cultured under static conditions or subjected to shear stress (either laminar or oscillatory flow). The impact of diabetes on YAP/TAZ signaling was additionally assessed in vivo in db/db mice.ResultsIn vitro, we found that YAP was dephosphorylated/activated by high glucose in endothelial cells, thus leading to increased endothelial inflammation and monocyte attachment. Moreover, YAP was further activated when high glucose was combined to laminar flow conditions. YAP was also activated by oscillatory flow conditions but, in contrast, high glucose did not exert any additional effect. Interestingly, inhibition of YAP reduced endothelial inflammation and monocyte attachment. Finally, we found that YAP is also activated in the vascular wall of diabetic mice, where inflammatory markers are also increased.ConclusionWith the current study we demonstrated that YAP signaling is activated by high glucose in endothelial cells in vitro and in the vasculature of diabetic mice, and we pinpointed YAP as a regulator of high glucose-mediated endothelial inflammation and monocyte attachment. YAP inhibition may represent a potential therapeutic opportunity to improve diabetes-associated vascular complications. |
Databáze: | OpenAIRE |
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