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Expression and distribution of meprin protease subunits in mouse intestine
1Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
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.
Insights
Meprin alpha, a protein subunit previously thought absent in mouse intestines, is now detected at low levels, increasing from duodenum to ileum. This suggests a specific intestinal function for meprins, varying by location and mouse strain.
Area of Science:
- Biochemistry
- Molecular Biology
- Gastroenterology
Background:
- Meprins are zinc metalloendopeptidases found in kidney and intestinal brush border membranes.
- They consist of alpha and beta subunits, with prior research indicating alpha subunit absence in mouse intestine.
Purpose of the Study:
- To investigate the presence and distribution of meprin alpha subunit mRNA and protein in mouse intestine.
- To compare meprin subunit expression across different intestinal segments and mouse strains.
Main Methods:
- Quantitative analysis of meprin alpha and beta subunit mRNA levels in mouse tissues (kidney, duodenum, jejunum, ileum, large intestine).
- Detection and comparison of meprin alpha protein expression along the intestinal tract.
- Assessment of intestinal meprin A activity and inhibitor response.
Main Results:
- Low levels of meprin alpha subunit mRNA and protein were detected in mouse small and large intestines.
- Meprin alpha expression increased longitudinally from duodenum to ileum, with ileum showing approximately 20% of kidney levels.
- Both ICR and C3H/He mouse strains showed detectable meprin alpha in the intestine, though at lower levels in C3H/He.
- Meprin beta subunit mRNA was consistently expressed in kidney and intestine, with higher levels in the ileum.
- Intestinal meprin activity and inhibitor response were consistent with kidney-derived meprin A.
Conclusions:
- Meprin alpha is present in the mouse small and large intestine, challenging previous assumptions.
- Meprin expression is tissue-specific, strain-specific, and longitudinally variable within the intestine.
- The expression patterns of both meprin alpha and beta subunits suggest a functional role in the ileum.