Indoxyl sulfate promotes the atherosclerosis through up-regulating the miR-34a expression in endothelial cells and vascular smooth muscle cells in vitro
| Autor: | Yaolin Yang, Yiqiao Zhao, Sen Chen, Fenghua Zhou, Zibin Lu, Wen Jin, Zhiqiu Xie, Xiaowei Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Physiology Myocytes Smooth Muscle Apoptosis 030204 cardiovascular system & hematology Muscle Smooth Vascular Umbilical vein 03 medical and health sciences 0302 clinical medicine Cell Movement Human Umbilical Vein Endothelial Cells Humans Chronic renal insufficiency In patient Viability assay Receptor Notch1 Cells Cultured Cell Proliferation Pharmacology Chemistry Atherosclerosis In vitro Up-Regulation MicroRNAs 030104 developmental biology Cancer research Molecular Medicine Indoxyl Sulfate Indican Signal Transduction |
| Zdroj: | Vascular Pharmacology. 131:106763 |
| ISSN: | 1537-1891 |
| DOI: | 10.1016/j.vph.2020.106763 |
| Popis: | Atherosclerosis (AS) is one of the most common cardiovascular events in patients with chronic renal insufficiency (CRI). During the development of CRI, uremic toxins, including indoxyl sulfate (IS), are pivotal risk factors for AS. However, the underlying mechanism between AS and IS has not been fully elucidated. The present study was designed to test our hypothesis that IS promotes the AS by regulating viability, proliferation, migration and apoptosis of endothelial cells and vascular smooth muscle cells. In this present study, our date showed that IS inhibited the cell viability of human umbilical vein endothelial cells (HUVECs) and human aortic vascular smooth muscle cells (HA-VSMCs) in a dose-dependent manner (P .05). Moreover, IS inhibited the proliferation, migration and induced apoptosis of HUVECs and HA-VSMCs significantly (P .05). However, inhibition of the miR-34a abolished these effects of IS in vitro, indicating that miR-34a is involved in the development of AS induced by IS. In addition, the luciferase reporter gene assay showed that up-regulating of miR-34a inhibited the Notch1 transcriptional activity remarkably (P .05). The expression of Notch1 decreased after IS treatment, while miR-34a inhibitor attenuated this effect. Moreover, the expression of miR-34a-related proteins Wnt-1, Jag1, E2F1 and SIRT1 decreased, while the expression of p53 increased in HUVECs and HA-VSMCs after IS treatment. Consistently, blockage of miR-34a abolished the remarkable effects on protein expressions induced by IS. Taken together, this study showed that IS can inhibit the proliferation, migration and promote apoptosis of HUVECs and HA-VSMCs through the Notch1 signal and miR-34a-related proteins by up-regulating miR-34a. These findings may provide new insights into the underlying mechanism of AS in CRI. |
| Databáze: | OpenAIRE |
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