| First Author | Herzog C | Year | 2007 |
| Journal | Kidney Int | Volume | 71 |
| Issue | 10 | Pages | 1009-18 |
| PubMed ID | 17377510 | Mgi Jnum | J:136906 |
| Mgi Id | MGI:3797327 | Doi | 10.1038/sj.ki.5002189 |
| Citation | Herzog C, et al. (2007) Role of meprin A in renal tubular epithelial cell injury. Kidney Int 71(10):1009-18 |
| abstractText | Meprins are zinc-dependent metalloproteinases that are highly expressed in the brush-border membranes of both the kidney and the intestines. Meprins are capable of proteolytically degrading extracellular matrix proteins, proteolytically processing bioactive proteins, and play a role in inflammatory processes. In this study, the function of meprin A in the acute kidney injury (AKI) model of cisplatin nephrotoxicity was examined. Normal linear localization of meprin A in the brush border membranes of proximal tubules was altered in AKI. The meprin A alpha-subunit was detected in the urine of both control and cisplatin-treated mice. A cleaved product of the meprin A beta-subunit, undetected in the urine of control mice, was found to be significantly increased in the urine during the progression of cisplatin nephrotoxicity. The excretion of this beta-fragment was found to be before the rise in serum creatinine and blood urea nitrogen (BUN) suggesting usefulness as a biomarker for AKI. Pretreatment of mice with a meprin A inhibitor afforded protection from cisplatin nephrotoxicity as reflected by significant decreases in serum creatinine, BUN, and the excretion of kidney injury molecule-1. These decreases in serum and urine biomarkers were accompanied by significant decreases in histologic markers such as leukocyte infiltration and apoptosis. Meprin A appears to be an important therapeutic target and urinary excretion appears to be a potential biomarker of AKI. |
