Expression and Activity of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in the Kidney of db/db Mice

[Objective] To study the pathogenic role of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in diabetic nephropathy by evaluating the expression and activity of MMPs- and TIMPs in the kidney of db/db mice. [Methods] Kidney tissues from 6 diabetic db/db mice were investigated. Protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was analyzed by western blot. The activity of MMP-2 and MMP-9 was measured by zymography. [Results] Protein expression of MMP-2 and MMP-9 in kidney of db/db mice was significantly lower than that in kidney of db/m mice (55. 4% and 30. 1% lower respectively, P 0. 05). The expression of both TIMP-1 and TIMP-2 proteins in kidney of db/db mice was significantly higher than that in db/m mice (272. 5% and 48. 8% higher, respectively, P 0. 01). The activity of MMP-9 in kidney of db/db mice was significantly lower than that in db/m mice (85. 9% lower, P 0. 001). The activity of MMP-2 was not detectable either in the kidney of db/db mice or db/m mice. [Conclusion] Decreased expression and activity of MMPs-and increased expression of TIMPs might contribute to the mesangial expansion characteristic of diabetic nephropathy in the kidney of db/db mice by decreasing extracellular matrix (ECM) degradation.