Regulation of the Proliferation of Diabetic Vascular Endothelial Cells by Degrading Endothelial Cell Functional Genes with QKI-7

Abstract

Background. 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. Purpose. 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. Methods. 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. Results. 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-α, IL-1β, and IFN-γ, leading to excessive proliferation of endothelial cells. After QKI-7 gene knockdown, the expression levels of CD144, NLGN1, and TSG6, inflammatory factors TNF-α, IL-1β, and IFN-γ, 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. Conclusion. 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.