Chengde Central Hospital, Chengde, Hebei 067000, China.
Department of Human Anatomy, Chengde Medical College, China.
Microvasc Res. 2022 Jan;139:104249. doi: 10.1016/j.mvr.2021.104249. Epub 2021 Sep 10.
Type I and II diabetes adversely affect the microvasculature of several organs, although the regulatory mechanisms remain unclear. Previous studies have found that differentially expressed circRNAs associated with hyperglycemia (HG) induce endothelial dysfunction. In the present study, high-throughput sequencing was employed to assess abnormal circRNA expression in human umbilical vein endothelial cells (HUVECs) after HG treatment. Then, bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation analysis, flow cytometry, and qRT-PCR analysis were performed to investigate the underlying regulatory mechanism and targets. The results demonstrate that hsa_circ_0022742 expression in HUVECs was decreased by HG treatment and overexpression of hsa_circ_0022742 suppressed HG-induced endothelial dysfunction. Luciferase analysis showed that miR-503-5p and FBXW7 were downstream targets of hsa_circ_0022742. Both overexpression of FBXW7 and inhibition of miR-503-5p reversed the protective effect of hsa_circ_0022742 against HG-induced endothelial dysfunction, including apoptosis, abnormal vascular differentiation, and secretion of inflammatory factors, indicating that hsa_circ_0022742 enhanced FBXW7 expression by sponging miR-503-5p. Taken together, these findings demonstrate that overexpression of hsa_circ_0022742 suppressed HG-induced endothelial dysfunction by targeting the miR-503-5p/FBXW7 axis.
一型和二型糖尿病会对多个器官的微血管造成不利影响，尽管调控机制尚不清楚。先前的研究发现，与高血糖（HG）相关的差异表达 circRNA 会诱导内皮功能障碍。在本研究中，我们采用高通量测序来评估 HG 处理后人脐静脉内皮细胞（HUVEC）中异常的 circRNA 表达。然后，进行生物信息学分析、荧光素酶报告分析、血管生成分化分析、流式细胞术和 qRT-PCR 分析，以研究潜在的调控机制和靶标。结果表明，HG 处理可降低 HUVEC 中 hsa_circ_0022742 的表达，而过表达 hsa_circ_0022742 可抑制 HG 诱导的内皮功能障碍。荧光素酶分析表明，miR-503-5p 和 FBXW7 是 hsa_circ_0022742 的下游靶标。过表达 FBXW7 和抑制 miR-503-5p 均可逆转 hsa_circ_0022742 对 HG 诱导的内皮功能障碍的保护作用，包括细胞凋亡、异常血管分化和炎症因子的分泌，表明 hsa_circ_0022742 通过海绵吸附 miR-503-5p 增强 FBXW7 的表达。综上所述，这些发现表明，过表达 hsa_circ_0022742 通过靶向 miR-503-5p/FBXW7 轴抑制 HG 诱导的内皮功能障碍。
