Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

Figure 7

Urinary and kidney network map. A biological network of interaction using 30 proteases and proteases inhibitor entries extrapolated from the respective arrays was analysed by KUPKB [38]. Selected proteins were 1.5-fold up- or downregulated with respect to the healthy control. According to their intracellular pathways, several proteases can bind and degrade also endogenous inhibitors. This type of binding and interactions can add further complexity to the respective networks, and proteolytic signals themselves may end up in multiple directions. Accordingly, cathepsin L inactivates serpinA1 [75] and MMPs can inactivate a variety of serpins [76]. Conversely, some cystatins interact with MMP-9, still preserving the catalytic function after autodegradation [77]. Interestingly, angiotensinogen (AGT) decreases, through the action of AGT II, the transcription of MMP-1, MMP-2, TIMP-1, TIMP-2, and TIMP-3 but increases MMP-9 in human cardiomyocytes [78].