Department of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China.
Contrast Media Mol Imaging. 2022 Jun 3;2022:6177809. doi: 10.1155/2022/6177809. eCollection 2022.
Diabetes has emerged as one of the most serious and common chronic diseases of our times, causing life-threatening, disabling and costly complications, and reducing life expectancy. Studies have shown that cardiovascular morbidity is 1-3 times higher in diabetic patients than in normal people. There are many clinical and experimental data that prove that most of the complications of diabetes are related to atherosclerosis, which suggests that chronic hyperglycemia may induce an imbalance in the proliferation of vascular endothelial cells.
This study aims to explore the relationship between QKI-7 and vascular endothelial cell dysfunction and lay a foundation for further clarifying the molecular mechanism of endothelial cell damage in the process of diabetes with atherosclerosis.
We chose blood samples and pluripotent stem cells and vascular endothelial cells of hospitalized patients with diabetes and diabetes atherosclerosis as research subjects. The expression levels of endothelial cell proliferation and genes related to endothelial cell proliferation were analyzed by RT-qPCR and Western blot, to study the influence of QKi-7 on the physiological state of endothelial cells. Through gene knockdown experiment, the effects of QKi-7 knockdown on functional genes and physiological functions of endothelial cells were analyzed. Finally, RNA immunoprecipitation was used to test the mutual effect among QKI-7 and the transcription level of functional genes, and the mRNA attenuation experiment proved that QKI-7 participated in the degradation process of functional genes.
The findings of the RT-qPCR and Western blot tests revealed that QKI-7 was highly expressed in blood samples of diabetic patients and atherosclerosis as well as in endothelial cells induced by human pluripotent stem cells and human vascular endothelial cells after high-glucose treatment. Overexpression and high glucose of QKI-7 resulted in inhibiting expressed function genes CD144, NLGN1, and TSG6 and upregulation of inflammatory factors TNF-, IL-1, and IFN-, leading to excessive proliferation of endothelial cells. After QKI-7 gene knockdown, the expression levels of CD144, NLGN1, and TSG6, inflammatory factors TNF-, IL-1, and IFN-, and the cell proliferation rate all returned to normal levels. RNA immunoprecipitation showed that QKi-7 interacted with CD144, NLGN1, and TSG6 mRNAs and was involved in the transcriptional degradation of functional genes through their interactions.
This research initially revealed the relevant molecular mechanism of QKI-7 leading to the excessive proliferation of endothelial cells in diabetic and atherosclerotic patients. In view of the role of QKI-7 in diabetic vascular complications, we provided a potential target for clinical diabetes treatment strategies in the future.
糖尿病已成为当今最严重和最常见的慢性疾病之一，可导致危及生命、使人丧失能力和代价高昂的并发症，并降低预期寿命。研究表明，糖尿病患者的心血管发病率比正常人高 1-3 倍。有许多临床和实验数据证明，糖尿病的大多数并发症都与动脉粥样硬化有关，这表明慢性高血糖可能导致血管内皮细胞增殖失衡。
本研究旨在探讨 QKI-7 与血管内皮细胞功能障碍的关系，为进一步阐明糖尿病伴动脉粥样硬化过程中内皮细胞损伤的分子机制奠定基础。
我们选择糖尿病和糖尿病伴动脉粥样硬化住院患者的血液样本和多能干细胞及血管内皮细胞作为研究对象。通过 RT-qPCR 和 Western blot 分析内皮细胞增殖和与内皮细胞增殖相关的基因表达水平，研究 QKi-7 对内皮细胞生理状态的影响。通过基因敲低实验，分析 QKi-7 敲低对内皮细胞功能基因和生理功能的影响。最后，采用 RNA 免疫沉淀试验检测 QKI-7 与功能基因转录水平之间的相互作用，并通过 mRNA 衰减实验证明 QKI-7 参与了功能基因的降解过程。
RT-qPCR 和 Western blot 检测结果显示，QKI-7 在糖尿病患者血液样本以及人多能干细胞诱导的内皮细胞和高糖处理后的人血管内皮细胞中高表达。QKI-7 的过表达和高糖导致抑制表达功能基因 CD144、NLGN1 和 TSG6，并上调炎症因子 TNF-、IL-1 和 IFN-，导致内皮细胞过度增殖。QKI-7 基因敲低后，CD144、NLGN1 和 TSG6 的表达水平、炎症因子 TNF-、IL-1 和 IFN-以及细胞增殖率均恢复正常水平。RNA 免疫沉淀显示，QKi-7 与 CD144、NLGN1 和 TSG6 的 mRNAs 相互作用，并通过相互作用参与功能基因的转录降解。
本研究初步揭示了 QKI-7 导致糖尿病和动脉粥样硬化患者内皮细胞过度增殖的相关分子机制。鉴于 QKI-7 在糖尿病血管并发症中的作用，为今后临床糖尿病治疗策略提供了一个潜在靶点。
