Active vitamin D reduces macrophage infiltration by TREM-1 in renal tissue of diabetic nephropathy rats / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effects of active vitamin D (VD) on the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in renal tissue of diabetic nephropathies (DN) rats and to explore the impact of TREM-1 on adhesion and migration capacity of macrophage.Methods DN rat models were established by streptozotocin.Rats were randomly distributed into four groupscontrol (NC) group,VD group,DN group and DN+VD group (DN rats with 0.1 μg · kg-1 · d-1 calcitriol by garages).Rats were sacrificed respectively at 8 weeks and 12 weeks after treatment.Pathological changes in kidney tissue were detected and the expressions of CD68 and TREM-1 were acquired by immunohistochemistry stain and Western blotting.In vitro,RAW264.7 cells were divided into NC group,VD group,high glucose (HG) group and HG+VD group.In HG+VD group rats were treated by high glucose with 10-8 mol/L 1,25(OH)2D3.TREM-1 expression was measured by immunohistochemistry stain and Western blotting,and the ability of macrophage in migration and adhesion was evaluated by Transwell migration assay and adhesion assay.TREM-1 siRNA was transferred to silence TREM-1 expression,while plasmid of TREM-1 was transferred for high expression.Their ability of adhesion and migration in macrophage and the effect of 1,25(OH)2D3 were examined.Results (1) Compared with the NC group,the expressions of CD68 and TREM-1 were increased in DN group (P ＜ 0.05),whereas markedly decreased in DN+VD group (P ＜ 0.05).(2) The number of adhesion and migration cells,and the expression of TREM-1 protein in macrophage were obviously increased in HG group as compared with those in NC group (all P ＜ 0.05);whereas above changes were markedly decreased in HG+VD group than those in HG group (P ＜ 0.05).(3) The number of adhesion and migrated macrophage was reduced after TREM-1 siRNA intervention (all P ＜ 0.05).VD could significantly decrease the effect of high glucose on adhesion and migrated macrophages after TREM-1 siRNA (all P ＜ 0.05).(4) Adhesion and migration of macrophage were increased via TREM-1 overexpression (all P ＜ 0.05),but the effects of VD on high glucose-induced adhesion and migration of macrophage were disappeared.Conclusions VD can suppress the adhesion and migration of macrophage via reducing the expression of TREM-1,and inhibit infiltration of macrophage in renal tissue of DN rats.