Objective To investigate the role of α₃β₁ integrin and α/β-dystroglycan in protective effects of 1,25(OH)₂D₃ on podocytes in rats with adriamycin-induced nephropathy.
Methods Sprague-Dawley rats were randomly divided into three groups: control group (NC), nephropathy group (NE), and nephropathy+1,25(OH)₂D₃ group (ND). Rats in NE and ND group were injected intravenously with adriamycin (0.1 mg/10 g body weight) to induce nephropathy, and those in ND group were then subcutaneously treated with 1,25(OH)₂D₃ for 8 weeks. Urinary protein level, number of urine podocytes, foot process width and glomerulosclerotic index were determined. Nephrin and podocin mRNA and protein expressions were determined by RT-PCR and western blot, respectively. Podocyte density and expressions of α₃β₁ integrin and α/β-dystroglycan (DG) were analyzed by immunohistochemistry and western blot, respectively.
Results The increase in proteinuria, podocyturia and width of foot process in NE group were ameliorated after treatment with 1,25(OH)₂D₃ for 8 weeks. The glomerulosclerotic index was significantly decreased in ND group when compared with NE group. The podocyte density in ND group (10.3 ± 1.64 cells/glomerulus) was significantly higher than that in NE group (8.43 ± 1.75 cells/glomerulus) (p=0.008). 1,25(OH)₂D₃ treatment could significantly up-regulate the mRNA and protein expressions of nephrin and podocin, and the protein expressions of α₃β₁ integrin and α/β-DG.
Conclusion The expressions of nephrin, podocin, α₃β₁ integrin and α/β-DG were decreased in rats with nephropathy. However, 1,25(OH)₂D₃ treatment could significantly up-regulate the expressions of nephrin, podocin, α₃β₁ integrin and α/β-DG proteins which might suppress podocyte detachment and podocytopenia.