High glucose-induced circHIPK3 downregulation mediates endothelial cell injury
- Nutrition Department, Kunshan Traditional Chinese Medicine Hospital, Kunshan (China)
- Nutrition Department, Bayi Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing (China)
Highlights: • CircHIPK3 downregulation in HG-treated HUVECs and diabetic patients' HAECs. • CircHIPK3 overexpression inhibits HG-induced endothelial cell death and apoptosis. • CircHIPK3 silencing exacerbates HG-induced endothelial cell death and apoptosis. • CircHIPK3 downregulation by HG induces miR-124 accumulation in endothelial cells. • MiR-124 inhibition protects endothelial cells from HG-induced cytotoxicity. High glucose (HG) induces vascular endothelial cell injury. However, the underlying mechanisms are poorly understood. Circular RNA HIPK3 (circHIPK3) is a highly conserved non-coding RNA. Here we show that circHIPK3 is downregulated in HG-treated human umbilical vein endothelial cells (HUVECs) and in primary aortic endothelial cells (HAECs) from diabetic patients. In both HUVECs and HAECs, lentivirus-mediated circHIPK3 overexpression inhibited HG-induced cell death and apoptosis. Contrarily, circHIPK3 silencing by targeted siRNA exacerbated HG-induced endothelial cell death and apoptosis. Further, circHIPK3 downregulation by HG caused microRNA-124 (miR-124) accumulation in HUVECs and HAECs. On the contrary, miR-124 inhibition by the adeno-associated virus (AAV)-packed miR-124 inhibitor protected endothelial cells from HG. Together, circHIPK3 downregulation mediates HG-induced endothelial cell injury. Targeting circHIPK3-miR-124 pathway could potentially be a novel approach for the treatment of diabetic-associated vascular injury.
- OSTI ID:
- 23134046
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1-4 Vol. 507; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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