Active vitamin D reduces macrophage infiltration by TREM-1 in renal tissue of diabetic nephropathy rats

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 groups: control (NC) group, VD group, DN group and DN+VD group (DN rats with 0.1 μg·kg-1·d-1 calcitriol by gavages). 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. Key words: Diabetic nephropathies; Receptors, immunologic; Cholecalciferol; Macrophages; Cell adhesion; Cell movement