Role of cathepsin B as prorenin processing enzyme in human kidney

Renin is synthesized from an inactive precursor, prorenin, through cleavage at a pair of basic amino acids catalyzed by prorenin processing enzyme (PPE). A lysosomal protease, cathepsin B, has been suggested to be a strong candidate for PPE. However, there still remains a possibility that other protease(s) can also catalyze prorenin processing. We studied the subcellular distribution of PPE in human renal cortex using pure recombinant prorenin as a PPE assay substrate. PPE and renin activities, and cathepsin B activity and protein were colocalized in the lysosomal fraction. The PPE activity was completely inhibited by a cathepsin B specific inhibitor, CA074. Taken together with the immunohistochemical data showing that cathepsin B and PPE are colocalized in dense secretory granules of juxtaglomerular cells of kidney, we conclude that cathepsin B is the authentic PPE in human kidney.