Division faculty members Andreas Herrlich, MD, PhD, Associate Professor of Medicine, and Eirini Kefaloyianni, PhD, Instructor of Medicine, today published a comprehensive manuscript describing the role of protease substrate release and kidney fibrosis. The study, published in JCI Insight, describes the upregulation of a disintegrin and metalloprotease 17 (ADAM17) during kidney disease. Substrates of this protease including pro-TNFα and the EGFR ligand amphiregulin (pro-AREG) are also upregulated and cleaved by ADAM17. Inducible knockout of ADAM17 in proximal tubule cells reduced inflammation and fibrosis, suggesting that therapeutic targeting of ADAM17 may be a viable novel therapeutic strategy in chronic kidney diseases.
The investigators also measured ADAM17 substrate levels in human urine from healthy volunteers or patients with kidney disease. Levels of AREG were remarkably upregulated in diseased urines, suggesting its possible utility as a biomarker of chronic kidney disease.