title: Meprin A metalloproteinase and its role in acute kidney injury.
abstract: Meprin A, composed of α- and β-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.
authors: Central Arkansas Veterans Healthcare System, 4300 West 7th St., 111D/LR, Little Rock, AR 72205, USA. Kaushalgurp@uams.edu
authors: Gur P
authors: GP
authors: Kaushal
authors: Randy S
authors: RS
authors: Haun
authors: Christian
authors: C
authors: Herzog
authors: Sudhir V
authors: SV
authors: Shah
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D002462:Cell Membrane / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000473:pathology / Q000502:physiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats
chemical_list: D008666:Metalloendopeptidases; C053833:meprin A
keywords: acute kidney injury; meprin; metalloproteinase; renal proximal tubule