MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in UUO
Copyright policy )MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in UUO
We examined the role of matrix metalloproteinase-2 (MMP-2) in renal fibrosis and its effect on interstitial macrophage infiltration in a mouse model of unilateral ureteral obstruction (UUO). TISAM, a selective inhibitor of MMP-2, was administered during early stage (day -2 to 4; protocol A) and late stage (day 7 to 13; protocol B) after UUO. Treatment with TISAM accelerated fibrosis both at day 5 (A) and at day 14 (B). The degree of macrophage infiltration was decreased by the treatment with TISAM at day 14, but not at day 5. In vitro macrophage migration assay showed a greater migration to renal tissue of control UUO kidney (day 14) than to TISAM-treated kidney, which was suppressed by preincubating macrophages with RGDS, a fibronectin degradation peptide. These results suggest that MMP-2 acts to accelerate macrophage infiltration in the late stage of UUO, possibly by degrading extracellular matrix components.
Male, Macrophages, Thiophenes, Macrophage Activation, Matrix Metalloproteinase Inhibitors, Kidney, Fibrosis, Mice, Inbred C57BL, Mice, Animals, Cell Aggregation, Ureteral Obstruction
Male, Macrophages, Thiophenes, Macrophage Activation, Matrix Metalloproteinase Inhibitors, Kidney, Fibrosis, Mice, Inbred C57BL, Mice, Animals, Cell Aggregation, Ureteral Obstruction
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