Expression of meprins in health and disease

Abstract

Publisher Summary The expression patterns of meprin subunits implicate meprins in embryogenesis, tissue-specific functions (especially for kidney, intestine, and leucocytes), and disease processes of cancer and inflammation. The abundance of meprins in brush border membranes and the multimeric nature of secreted isoforms indicate that localized high concentrations of latent and activated proteases are fundamental to the action of these metalloproteinases. The enzymes are highly regulated transcriptionally and posttranslationally, indicating that they have specific functions and are not general “housekeeping” proteases, and are targeted to specific sites of action. A base of knowledge exists about the structure/function of the meprins and about potential physiological substrates for the enzymes. Information provided by genomics, the mouse and human genome projects, microarray analysis, molecular modeling, and high-throughput technologies reveals new sites of expression of the meprins (prostate and pancreatic cells), about the enzymatic activities, and the potential contributions of these enzymes to the degradation and activation of peptides and proteins at the cell surface and in extracellular compartments. The creation of specific inhibitors of meprins and of genetically engineered mice and the identification of polymorphisms in the meprin genes and regulatory elements for the genes help decipher functions of the enzyme in vivo and further define the role of these enzymes in heath and disease.