[WD40 repeat-containing protein 6 aggravates diabetic kidney disease by promoting lipid accumulation in kidney].

OBJECTIVES

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).

CONCLUSIONS

Elevated WDR6 levels may affect renal lipid metabolism, thereby accelerating the pathological progression of DKD.