دورية أكاديمية
Indoxyl Sulfate-Induced Valve Endothelial Cell Endothelial-to-Mesenchymal Transition and Calcification in an Integrin-Linked Kinase-Dependent Manner
| العنوان: | Indoxyl Sulfate-Induced Valve Endothelial Cell Endothelial-to-Mesenchymal Transition and Calcification in an Integrin-Linked Kinase-Dependent Manner |
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| المؤلفون: | Maria Delgado-Marin, Sandra Sánchez-Esteban, Alberto Cook-Calvete, Sara Jorquera-Ortega, Carlos Zaragoza, Marta Saura |
| المصدر: | Cells, Vol 13, Iss 6, p 481 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | valve endothelial cells, calcific valve disease, chronic kidney disease, indoxyl sulfate, cell transdifferentiation, integrin-linked kinase, Cytology, QH573-671 |
| الوصف: | Calcific Aortic Valve Disease (CAVD) is a significant concern for cardiovascular health and is closely associated with chronic kidney disease (CKD). Aortic valve endothelial cells (VECs) play a significant role in the onset and progression of CAVD. Previous research has suggested that uremic toxins, particularly indoxyl sulfate (IS), induce vascular calcification and endothelial dysfunction, but the effect of IS on valve endothelial cells (VECs) and its contribution to CAVD is unclear. Our results show that IS reduced human VEC viability and increased pro-calcific markers RUNX2 and alkaline phosphatase (ALP) expression. Additionally, IS-exposed VECs cultured in pro-osteogenic media showed increased calcification. Mechanistically, IS induced endothelial-to-mesenchymal transition (EndMT), evidenced by the loss of endothelial markers and increased expression of mesenchymal markers. IS triggered VEC inflammation, as revealed by NF-kB activation, and decreased integrin-linked kinase (ILK) expression. ILK overexpression reversed the loss of endothelial phenotype and RUNX2, emphasizing its relevance in the pathogenesis of CAVD in CKD. Conversely, a lower dose of IS intensified some of the effects in EndMT caused by silencing ILK. These findings imply that IS affects valve endothelium directly, contributing to CAVD by inducing EndMT and calcification, with ILK acting as a crucial modulator. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 13060481 2073-4409 |
| العلاقة: | https://www.mdpi.com/2073-4409/13/6/481Test; https://doaj.org/toc/2073-4409Test |
| DOI: | 10.3390/cells13060481 |
| الوصول الحر: | https://doaj.org/article/57cba92b68024a8297406e44c62f7aa3Test |
| رقم الانضمام: | edsdoj.57cba92b68024a8297406e44c62f7aa3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 13060481 20734409 |
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| DOI: | 10.3390/cells13060481 |