Abstract:
Background Cadmium is a major environmental pollutant, and can induce damage to human health at low levels. Kidney is one of the target organs of cadmium. However, the mechanism of renal impairment caused by cadmium exposure is not clear yet.
Objective This study is designed to evaluate the relationship of low-level environmental cadmium exposure with plasma transforming growth factor (TGF)-β1/Smad3, related microRNAs (miRNA), and kidney injury.
Methods A total of 223 community residents from a village irrigated with cadmium polluted water were selected as exposed group, and 237 community residents from a village 32 km away from the polluted area and not irrigated with cadmium polluted water were selected as control group. A face-to-face questionnaire survey was conducted to collect general information of the residents from cadmium polluted and non-polluted areas. Fasting venous blood samples were collected to detect plasma TGF-β1 and Smad3, and urinary samples were also collected to detect urinary N-acetyl-beta-D-glucosaminidase (UNAG), albumin (UALB), kidney injury molecule-1 (UKim-1), and cadmium. The associations among urinary cadmium, plasma TGF-β1/Smad3, and kidney injury were analyzed. The expressions of miRNAs between cadmium exposure with kidney damage group and control group were compared by 1:1 matched casecontrol design.
Results The urinary cadmium level of the exposed group (1.06 μg/g, adjusted by urinary creatinine, thereafter) was higher than that of the control group (0.74 μg/g) (P < 0.001). Compared with the control group, the levels of plasma TGF-β1, plasma Smad3, UNAG, and UALB were significantly higher in the exposed group (P < 0.05). With the increasing of age, the levels of UNAG and UALB in the exposed group and the levels of UNAG and UKim-1 in the control group increased significantly (Ptrend < 0.01). The Pearson correlation analysis results showed that plasma TGF-β1 had a positive correlation with UNAG and plasma Smad3 (r=0.133, P < 0.001; r=0.091, P < 0.05). The regression analysis results showed that urinary cadmium was closely associated with UNAG (b=0.285, 95% CI:0.076-0.494), UALB (b=0.738, 95% CI:0.385-1.092), and UKim-1 (b=0.038, 95% CI:0.014-0.062). The expression levels of miRNA-21, miRNA-192, and miRNA-126 were higher in the cadmium exposure and kidney damage group than those of the control group.
Conclusion The levels of peripheral blood TGF-β1 and Smad3 are increased among the participants with low-level environmental exposure to cadmium. The increasing expression levels of miRNA-21, miRNA-192, and miRNA-126 might be involved in the renal impairment associated with cadmium exposure.
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