浙江大学学报（医学版）2026，Vol.55Issue(5)：465-474,10.DOI:10.3724/zdxbyxb-2025-0666
WD40重复结构域蛋白6影响肾脏脂质代谢促进糖尿病肾病进展
WD40 repeat-containing protein 6 aggravates diabetic kidney disease by promoting lipid accumulation in kidney
摘要
Abstract
Objective:To investigate the role and mechanism of WD40 repeat-containing protein 6(WDR6)in the regulation of renal lipid metabolism and its involvement in the progression of diabetic kidney disease(DKD).Methods:A total of 97 patients who underwent renal biopsy in Linyi People's Hospital between 2015 and 2023 were enrolled.Based on pathological diagnoses,the patients were divided into three groups:non-DKD(n=38),DKD stage Ⅱ(n=24),and DKD stage Ⅲ(n=35).Clinical indicators,including complete blood count,liver and kidney function tests,and markers of glucose and lipid metabolism,were assessed.Renal tissue damage was evaluated by renal biopsy pathology.Immunohistochemistry was used to detect the expressions of WDR6 and adipose differentiation-related protein(ADRP).Human renal tubular epithelial(HK-2)cells were stimulated with high glucose,and lipid deposition was observed by oil red O staining.Protein and mRNA levels of lipid metabolism-related molecules were measured by Western blotting and qRT-PCR.Additionally,the effect of small interfering RNA-mediated WDR6 silencing on the above indicators was examined.Results:Compared with the non-DKD group,DKD stage Ⅱ and DKD stage Ⅲ groups exhibited significant abnormalities in renal function-and lipid metabolism-related parameters,along with varying degrees of renal tissue injury.WDR6 was expressed in human kidney,and its expression together with ADRP was elevated in the DKD groups(both P<0.01).After 48 hours of high-glucose stimulation,HK-2 cells exhibited prominent lipid deposition,accompanied by increased protein and mRNA levels of WDR6,ADRP,sterol regulatory element-binding protein 1(SREBP1),and fatty acid synthase compared with the blank control group(all P<0.01).Silencing WDR6 reduced high glucose-induced lipid deposition and the expression of these lipid metabolism-related molecules(all P<0.05).Conclusion:Elevated WDR6 levels may affect renal lipid metabolism,thereby accelerating the pathological progression of DKD.关键词
糖尿病肾脏病/WD40重复结构域蛋白6/脂质代谢/人肾小管上皮细胞Key words
Diabetic kidney disease/WD40 repeat-containing protein 6/Lipid metabolism/Human renal tubular epithelial cells分类
医药卫生引用本文复制引用
辛培青,孙丽娜,牛少娜,孙雪..WD40重复结构域蛋白6影响肾脏脂质代谢促进糖尿病肾病进展[J].浙江大学学报（医学版）,2026,55(5):465-474,10.基金项目
山东第二医科大学附属医院科研发展基金(2025FYM053)This study was supported by Shandong Second Medical University Affiliated Hospital Scientific Research Development Fund(2025FYM053) （2025FYM053）
