Li Changhao, Dong Fuda, Dilixiati Yilimilai, Bai Yunbin, Zhang Zengli
School of Public Health, Soochow University, 199 Renai Road, Suzhou, 215123, Jiangsu, China.
Tianjin Center for Disease Control and Prevention, No. 6 Huayue Road, Hedong District, Tianjin, 300011, China.
Lipids Health Dis. 2025 Aug 13;24(1):262. doi: 10.1186/s12944-025-02557-y.
Cadmium (Cd) is a heavy metal with nephrotoxicity. While the harmful effects of Cd exposure on the kidney have been extensively studied, the nephrotoxicity of Cd exposure on diabetic individual remain largely unexplored. Given the widespread Cd pollution and the high prevalence of diabetes, it is imperative to explore the nephrotoxicity and underlying mechanism of Cd exposure on diabetic individual.
In current study, established diabetic mouse and high glucose cultured HK-2 cells were exposed to CdCl (50 ppm in vivo, 10 µM in vitro). Renal fibrosis and renal lipid accumulation were studied in Cd-exposed diabetic mice and high glucose cultured HK-2 cells. Additionally, qRT-PCR and Western blot were used to evaluate renal fibrosis and lipid metabolism related gene and protein.
Present study showed no significant nephrotoxicity in Cd-exposed healthy mice and Cd-exposed HK-2 cells. However, same dosing Cd activated TGF/SMAD signaling pathway and increased collagen deposition in kidney of diabetic mice and high glucose cultured HK-2 cells. Intriguingly, Cd reduced renal lipids deposition and inhibited fatty acid synthesis both in diabetic mice and high glucose cultured HK-2 cells.
Overall, our findings demonstrate that low dosing Cd significantly aggravated renal fibrosis in diabetic mice and high glucose cultured HK-2 cells. It is recommended that diabetic individuals should avoid working in Cd pollution environment and consuming cadmium-contaminated food. Furthermore, we found that Cd reduced lipid deposition in kidney of diabetic mice and high glucose cultured HK-2 cells. The results provide novel insights into renal lipid metabolism in Cd-exposed diabetic individuals.
镉（Cd）是一种具有肾毒性的重金属。虽然镉暴露对肾脏的有害影响已得到广泛研究，但镉暴露对糖尿病个体的肾毒性在很大程度上仍未被探索。鉴于镉污染的广泛存在和糖尿病的高患病率，探索镉暴露对糖尿病个体的肾毒性及其潜在机制势在必行。
在本研究中，将已建立的糖尿病小鼠和高糖培养的HK-2细胞暴露于氯化镉（体内50 ppm，体外10 μM）。对镉暴露的糖尿病小鼠和高糖培养的HK-2细胞进行肾纤维化和肾脂质蓄积研究。此外，采用qRT-PCR和蛋白质免疫印迹法评估肾纤维化和脂质代谢相关基因及蛋白。
本研究表明，镉暴露的健康小鼠和镉暴露的HK-2细胞未显示出明显的肾毒性。然而，相同剂量的镉激活了糖尿病小鼠肾脏和高糖培养的HK-2细胞中的TGF/SMAD信号通路，并增加了胶原蛋白沉积。有趣的是，镉在糖尿病小鼠和高糖培养的HK-2细胞中均减少了肾脂质沉积并抑制了脂肪酸合成。
总体而言，我们的研究结果表明，低剂量镉显著加重了糖尿病小鼠和高糖培养的HK-2细胞的肾纤维化。建议糖尿病个体应避免在镉污染环境中工作以及食用受镉污染的食物。此外，我们发现镉减少了糖尿病小鼠肾脏和高糖培养的HK-2细胞中的脂质沉积。这些结果为镉暴露的糖尿病个体的肾脂质代谢提供了新的见解。
