| First Author | Kaushal GP | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 304 |
| Issue | 9 | Pages | F1150-8 |
| PubMed ID | 23427141 | Mgi Jnum | J:197268 |
| Mgi Id | MGI:5491989 | Doi | 10.1152/ajprenal.00014.2013 |
| Citation | Kaushal GP, et al. (2013) Meprin A metalloproteinase and its role in acute kidney injury. Am J Physiol Renal Physiol 304(9):F1150-8 |
| abstractText | Meprin A, composed of alpha- and beta-subunits, is a membrane-associated neutral metalloendoprotease that belongs to the astacin family of zinc endopeptidases. It was first discovered as an azocasein and benzoyl-l-tyrosyl-p-aminobenzoic acid hydrolase in the brush-border membranes of proximal tubules and intestines. Meprin isoforms are now found to be widely distributed in various organs (kidney, intestines, leukocytes, skin, bladder, and a variety of cancer cells) and are capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins. The ability of meprin A to cleave various substrates sheds new light on the functional properties of this enzyme, including matrix remodeling, inflammation, and cell-cell and cell-matrix processes. Following ischemia-reperfusion (IR)- and cisplatin-induced acute kidney injury (AKI), meprin A is redistributed toward the basolateral plasma membrane, and the cleaved form of meprin A is excreted in the urine. These studies suggest that altered localization and shedding of meprin A in places other than the apical membranes may be deleterious in vivo in acute tubular injury. These studies also provide new insight into the importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions. Meprin A is injurious to the kidney during AKI, as meprin A-knockout mice and meprin inhibition provide protective roles and improve renal function. Meprin A, therefore, plays an important role in AKI and potentially is a unique target for therapeutic intervention during AKI. |
