التفاصيل البيبلوغرافية
| العنوان: |
High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction |
| المؤلفون: |
Gurinder Bir Singh, Yang Zhang, Krishna M. Boini, Saisudha Koka |
| المصدر: |
International Journal of Molecular Sciences; Volume 20; Issue 14; Pages: 3570 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2019 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
HMGB1, TMAO, tight junction, ZO2, glycyrrhizin |
| جغرافية الموضوع: |
agris |
| الوصف: |
The intestinal microbe-derived metabolite trimethylamine N-oxide (TMAO) is implicated in the pathogenesis of cardiovascular diseases (CVDs). The molecular mechanisms of how TMAO induces atherosclerosis and CVDs’ progression are still unclear. In this regard, high-mobility group box protein 1 (HMGB1), an inflammatory mediator, has been reported to disrupt cell–cell junctions, resulting in vascular endothelial hyper permeability leading to endothelial dysfunction. The present study tested whether TMAO associated endothelial dysfunction results via HMGB1 activation. Biochemical and RT-PCR analysis showed that TMAO increased the HMGB1 expression in a dose-dependent manner in endothelial cells. However, prior treatment with glycyrrhizin, an HMGB1 binder, abolished the TMAO-induced HMGB1 production in endothelial cells. Furthermore, Western blot and immunofluorescent analysis showed significant decrease in the expression of cell–cell junction proteins ZO-2, Occludin, and VE-cadherin in TMAO treated endothelial cells compared with control cells. However, prior treatment with glycyrrhizin attenuated the TMAO-induced cell–cell junction proteins’ disruption. TMAO increased toll-like receptor 4 (TLR4) expression in endothelial cells. Inhibition of TLR4 expression by TLR4 siRNA protected the endothelial cells from TMAO associated tight junction protein disruption via HMGB1. In conclusion, our results demonstrate that HMGB1 is one of the important mediators of TMAO-induced endothelial dysfunction. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms20143570 |
| DOI: |
10.3390/ijms20143570 |
| الاتاحة: |
https://doi.org/10.3390/ijms20143570 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.5CB34764 |
| قاعدة البيانات: |
BASE |