Expression and Distribution of Meprin Protease Subunits in Mouse Intestine

Meprins, zinc metalloendopeptidases of kidney and intestinal brush border membranes, are composed of differing ratios of α and β subunits. Previous work indicated that the β subunit was expressed in kidney and intestine of all mouse strains, but that the α 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 α 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 α mRNA (μg/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 β subunits in kidney and intestine, displayed very low levels of meprin α mRNA (approximately 1% of that in ICR kidney) in both the kidney and intestine. Intestinal meprin β 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 β message in the ileum relative to duodenum or jejunum. In general, the pattern of the meprin α protein along the intestine was similar to that of α mRNA, and activity and response of intestinal meprin A to inhibitors were typical of the enzyme isolated from kidney. These data indicate that meprin α 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 α and β subunits indicates an ileal function for the meprins.