Various effects of ADAM10 and ADAM17 metalloproteases on kidney (dys)function.

A disintegrin and metalloprotease 10 (ADAM10) and ADAM17 regulate cellular communication by shedding membrane-bound proteins. They participate in numerous physiological processes, e.g. contribute to proper glomerular filtration maintenance. Because of their broad substrate specificity, their activity is tightly regulated and dependent on the local tissue microenvironment, including blood glucose fluctuations. The dysregulation of ADAM10/17-mediated shedding has been associated with the development of several kidney diseases. Increases in ADAM10/17 mRNA, protein levels, and activity have been reported in renal disorders, suggesting their possible application as indicators of renal involvement in systemic diseases. Serum and urinary levels of soluble ADAM10/17 substrates, shed from resident kidney cells, may serve as early biomarkers of renal dysfunction. ADAM10/17 have also emerged as potential therapeutic targets in renal diseases. Thus, the present review summarizes current knowledge of the various roles ADAM10/17 perform in kidney physiology and pathophysiology, with a particular emphasis on diabetic kidney disease.