糖尿病肾病中环状RNA circHIPK3的表达和生物学作用分析

Analysis of the Expression and Biological Role of circHIPK3 in Diabetic Nephropathy

目的:探讨和分析糖尿病肾病中环状RNA circHIPK3的表达和生物学作用。方法:回顾性收集2017年01月—2020年06月来我院就诊的糖尿病肾病患者90例,同期收集体检健康的志愿者30例,分别提取两组研究对象外周血RNA,检测两组circHIPK3的表达差异,并分析其表达水平与蛋白尿、空腹血糖、糖化血红蛋白和三酰甘油等病理指标的相关性。以肾系膜细胞SV40-MES13为研究对象,沉默circHIPK3,观察其增殖、侵袭和纤维化水平的变化,并对其分子机制进行探索。结果:糖尿病肾病患者外周血circHIPK3的表达水平明显高于正常对照组(P<0.001),大量蛋白尿患者外周血circHIPK3的表达水平亦高于微量蛋白尿组(P<0.001),circHIPK3的表达水平和蛋白尿、空腹血糖、糖化血红蛋白、三酰甘油等糖尿病肾病的临床病理参数均存在明显的正相关性(P<0.05)。circHIPK3沉默后,细胞活力、侵袭力和纤维化相关指标胶原蛋白Ⅰ、胶原蛋白Ⅳ和纤连蛋白的表达水平均明显降低,进一步的机制研究发现circHIPK3具有miR-508-3p吸附作用。结论:糖尿病肾病中存在显著的circHIPK3高表达,circHIPK3通过miR-508-3p吸附作用可促进系膜细胞增殖、侵袭和肾脏纤维化。

Objective:To investigate and analyze the expression and biological role of circHIPK3 in diabetic nephropathy.Methods:90 cases of patients with diabetic nephropathy were collected between January 2017 and June 2020 in our hospital,in the same period 30 cases of healthy volunteers were collected.RNA was extracted from peripheral blood of the two groups,and the expression of circHIPK3 was detected,and the correlation between the expression level and pathological indexes such as proteinuria,fasting blood glucose,glycosylated hemoglobin and triglyceride was analyzed.Taking renal mesangial cell sv40-mes13 as the research object,circhipk3 was silenced,the changes of proliferation,invasion and fibrosis were observed,and its molecular mechanism was explored.Results:The expression level of circHIPK3 in peripheral blood of patients with diabetic nephropathy was significantly higher than that of the normal control group(P<0.001).The expression level of circHIPK3 in the peripheral blood of patients with massive proteinuria was also higher than that in the microalbuminuria group(P<0.001),and the expression level of circHIPK3,proteinuria,fasting blood glucose,glycosylated hemoglobin,and so on.There was a significant positive correlation between triglycerides and other clinical pathological parameters of diabetic nephropathy(P<0.05).After circhipk3 silencing,the expression levels of collagenⅠ,collagenⅣand fibronectin decreased significantly.Further mechanism study found that circhipk3 had mir-508-3p adsorption.Conclusion:CircHIPK3 is highly expressed in diabetic nephropathy,which can promote mesangial cell proliferation,invasion and renal fibrosis through mir-508-3p adsorption.