Expression and distribution of meprin protease subunits in mouse intestine

Abstract

Meprins, zinc metalloendopeptidases of kidney and intestinal brush border membranes, are composed of differing ratios of alpha and beta subunits. Previous work indicated that the beta subunit was expressed in kidney and intestine of all mouse strains, but that the alpha subunit was only expressed in kidney of random-bred and some inbred strains and not in mouse intestine. The work herein, however, reports that low levels of meprin alpha subunit mRNA and protein are detectable in mouse intestine and are present in increasing concentrations from the duodenum to the ileum. In ICR mice, the duodenum expressed less than 1% of the meprin alpha mRNA (micrograms/g tissue) relative to kidney, the ileum approximately 20%. The large intestine contained approximately 10% of the message found in kidney. An inbred mouse strain, C3H/He, found previously to contain only meprin beta subunits in kidney and intestine, displayed very low levels of meprin alpha mRNA (approximately 1% of that in ICR kidney) in both the kidney and intestine. Intestinal meprin beta mRNA in ICR and C3H/He mice, by contrast, was expressed at similar levels to that found in kidney, and for both strains there was an increase (two- to threefold) in the beta message in the ileum relative to duodenum or jejunum. In general, the pattern of the meprin alpha protein along the intestine was similar to that of alpha mRNA, and activity and response of intestinal meprin A to inhibitors were typical of the enzyme isolated from kidney. These data indicate that meprin alpha can be detected in mouse small and large intestine and that expression is not only tissue- and strain-specific but also longitudinally variable in intestine. The expression pattern for both a and beta subunits indicates an ileal function for the meprins.