Figure 4
Effect of cinaciguat on the expression of renal extracellular matrix turnover components. (a) Compared to the non-diabetic controls, MMP-9 mRNA expression was markedly reduced in DM kidneys, accompanied by 4-fold increased TIMP-1 expression. Although cinaciguat did not alter MMP-9 expression, it attenuated TIMP-1 overexpression, which resulted in slightly better MMP-9/TIMP-1 ratio in DM-Cin kidneys, as compared to DM, supported by the MMP-9 zymography results. (b) The renal mRNA expression of MMP-2 dropped in DM rats, but was normalized in DM-Cin group. TIMP-2 mRNA expression reduced in both DM and DM-Cin groups, but the MMP-2/TIMP-2 imbalance was attenuated in DM-Cin kidneys. Zymography did not show, in contrast, significant changes in MMP-2 activity. Representative zymogram bands are shown. The mRNA expression was normalized for GAPDH expression using the formula 2 −ΔΔCt. Data are presented as mean ± SD (n = 8–10/group). *p < 0.05, **p < 0.01, ***p < 0.001 (two-way ANOVA with Sidak’s multiple comparison test).
