Effects of 1,25-dihydroxyvitamin D3 on the expression of vitamin D receptor and related factors in diabetic nephropathy

Abstract

Objective To explore the effects and mechanism of 1,25-dihydroxyvitamin D3 on the diabetic nephropathy with different levels of vitamin D receptor (VDR) expression in rats. Methods The models of diabetic nephropathy SD rats (n=36) were established by intraperitoneal injection of streptozotoein, then the rat models were divided into 3 groups: VDR over-expression group (kidney injection of VDR virus, n=12), VDR normal expression group (kidney injection of viral vector, n=12) and VDR low expression group (kidney injection of VDR interfered virus, n=12). Then the rats in the three groups were given calcitriol (0.03 μg·kg-1·d-1) or peanut oil for 37 days, six rats with one treatment in each group. So the rats were divided into 6 groups: VDR over-expression+VD group, VDR over-expression+peanut oil group, VDR low expression+VD group, VDR low expression+peanut oil group, VDR normal expression+VD group, VDR normal expression+peanut oil group. The real time-polymerase chain reaction (RT-PCR) and immunohistochemistry staining were used to detect the mRNA and protein levels of VDR, transforming growth factor(TGF)-β1, phosphatase and tensin homolog deleted on chromosome ten (PTEN), cologen-1(COL-1) in kidney. And the HE and Masson staining were used to detect changes of structure and the level of fibrosis in kidney. Data were compared by using t-test and one-way analysis of variance. Results The expressions of VDR and PTEN mRNA and protein in VDR over-expression+VD group were significantly higher than those in VDR over-expression+peanut oil group (t=-19.67, -5.18, -25.57, -10.06, all P<0.01). The expressions of TGF-β1 and COL-1 mRNA and protein in VDR over-expression+VD group significantly decreased than those in VDR over-expression+peanut oil group(t=15.62, 8.20, 28.28, 5.81, all P<0.01). The expressions of VDR and PTEN mRNA and protein in VDR low-expression+VD group were significantly higher than those in VDR low-expression+peanut oil group (t=-53.67, -7.00, -19.81, -8.06, all P<0.01). The expressions of TGF-β1 and COL-1 mRNA and protein in VDR low-expression+VD group decreased significantly than those in VDR low-expression+peanut oil group(t=12.00, 8.50, 21.22, 5.42, all P<0.01). The expressions of VDR and PTEN mRNA and protein in VDR normal expression+VD group were significantly higher than those in VDR normal expression+peanut oil group (t=-20.39, -5.46, -25.92, -6.38, all P<0.01). The expression of TGF-β1 and COL-1 mRNA and protein in VDR normal expression+VD group significantly decreased than those in VDR normal expression+peanut oil group (t=17.80, 10.61, 47.36, 8.23, all P<0.01). The pathological structure of the kidney in kidney disorders was associated with the low levels of VDR. These fibrosis changes could be improved by calcitriol interventions. Conclusions The 1,25-dihydroxyvitamin D3 has some anti-fibrosis effects on diabetic nephropathy by the pathway of VDR in kidney. Key words: Diabetic nephropathy; 1,25-dihydroxy vitamin D3; Vitamin D Receptor; Transforming growth factor-β1