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Hyperglycemia- Induced NF-κB Activation Increases microRNA-146a Expression in Human Umbilical Vein Endothelial Cells
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Elnaz Salmani Korjan    , Kamila Kamali , Majid Katebi , Afshin Samiei , Farhad Ghadiri Soufi * |
| Molecular Medicine Research Center, Health institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. , dr.f.g.soufi@gmail.com |
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Abstract: (5528 Views) |
Background & objectives: Nuclear Factor kappa B (NF-κB), a master switch transcription factor, plays a critical role in the progression and development of hyperglycemia-induced microangiopathy. Hyperglycemia activates NF-κB, and subsequently increases pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β leading to development of inflammation. Some new studies have revealed the involvement of microRNA-146a (miR-146a) in the pathogenesis of diabetic complications through an NF-κB-dependent negative feedback loop manner. Despite numerous reports indicating changes of plasma miR-146a during hyperglycemia, the origin of this change remains unclear. This study was designed to evaluate the role of NF-κB on the miR-146a gene expression level in human umbilical vein endothelial cells (HUVECs) during a hyperglycemic condition.
Methods: HUVECs were cultured in normal glucose (5 mmol/L), and hyperglycemic (25 mmol/L) endothelial cell growth medium in the six well plates for 24 h. JSH-23 (30 μmol/L), as an inhibitor of NF-κB translocation to the nucleus, was added to the culture medium, 30 min before induction of hyperglycemia. Quantitative Real Time PCR was performed to measure the expression levels of miR-146a and mRNA NF-κB. NF-κB activity was measured by Elisa.
Results: Hyperglycemia markedly increased the NF-κB activity and mRNA level in HUVECs. The expression of miR-146a significantly increased in hyperglycemic group compared to the normoglycemic group. On the other hand, JSH-23 prevented from miR-146a increment in hyperglycemic group and also it increased the mRNA expression level of NF-κB in this group.
Conclusion: This result shows that NF-κB increases the gene expression of miRNA-146a in the early phase of hyperglycemia in HUVECs.
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| Keywords: Nuclear Factor- κB, Hyperglycemia, HUVECs, miR-146a |
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Full-Text [PDF 230 kb]
(2889 Downloads)
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Type of Study: article |
Subject:
Physiology
Received: 2018/12/21 | Accepted: 2019/03/11 | Published: 2019/03/30
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