Role of SGK1 in the Osteogenic Transdifferentiation and Calcification of Vascular Smooth Muscle Cells Promoted by Hyperglycemic Conditions
| Autor: | Florian Poetsch, Barbara Moser, Kai-Uwe Eckardt, Ioana Alesutan, Laura A Henze, Jakob Voelkl, Florian Lang, Burkert Pieske, Misael Estepa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Glycation End Products
Advanced 0301 basic medicine Vascular smooth muscle osteogenic transdifferentiation Muscle Smooth Vascular NF-κB lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine Osteogenesis Glycation vascular smooth muscle cells NF-kB SGK1 lcsh:QH301-705.5 Aorta Spectroscopy Gene knockdown Chemistry Kinase advanced glycation end products Transdifferentiation Calcinosis General Medicine Computer Science Applications high glucose Hydrazines vascular calcification 030220 oncology & carcinogenesis Benzamides diabetes mellitus cardiovascular system Signal Transduction medicine.medical_specialty Myocytes Smooth Muscle Primary Cell Culture Protein Serine-Threonine Kinases Article Catalysis Immediate-Early Proteins Inorganic Chemistry 03 medical and health sciences Internal medicine medicine Humans Physical and Theoretical Chemistry Molecular Biology urogenital system Organic Chemistry medicine.disease Glucose 030104 developmental biology Endocrinology lcsh:Biology (General) lcsh:QD1-999 Hyperglycemia Cell Transdifferentiation Calcification |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 19 International Journal of Molecular Sciences, Vol 21, Iss 7207, p 7207 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21197207 |
| Popis: | In diabetes mellitus, hyperglycemia promotes the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) to enhance medial vascular calcification, a common complication strongly associated with cardiovascular disease and mortality. The mechanisms involved are, however, still poorly understood. Therefore, the present study explored the potential role of serum- and glucocorticoid-inducible kinase 1 (SGK1) during vascular calcification promoted by hyperglycemic conditions. Exposure to high-glucose conditions up-regulated the SGK1 expression in primary human aortic VSMCs. High glucose increased osteogenic marker expression and activity and, thus, promoted the osteogenic transdifferentiation of VSMCs, effects significantly suppressed by additional treatment with the SGK1 inhibitor EMD638683. Moreover, high glucose augmented the mineralization of VSMCs in the presence of calcification medium, effects again significantly reduced by SGK1 inhibition. Similarly, SGK1 knockdown blunted the high glucose-induced osteogenic transdifferentiation of VSMCs. The osteoinductive signaling promoted by high glucose required SGK1-dependent NF-κB activation. In addition, advanced glycation end products (AGEs) increased the SGK1 expression in VSMCs, and SGK1 inhibition was able to interfere with AGEs-induced osteogenic signaling. In conclusion, SGK1 is up-regulated and mediates, at least partly, the osteogenic transdifferentiation and calcification of VSMCs during hyperglycemic conditions. Thus, SGK1 inhibition may reduce the development of vascular calcification promoted by hyperglycemia in diabetes. |
| Databáze: | OpenAIRE |
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