THE METALLOPROTEINASE MATRILYSIN IS PREFERENTIALLY EXPRESSED BY EPITHELIAL-CELLS IN A TISSUE-RESTRICTED PATTERN IN THE MOUSE

To explore the role of the matrix metalloproteinase matrilysin (MAT) i n normal tissue remodeling, we cloned the murine homologue of MAT from postpartum uterus using RACE polymerase chain reaction and examined i ts pattern of expression in embryonic, neonatal, and adult mice. The m urine coding sequence and the corresponding predicted protein sequence were found to be 75% and 70% identical to the human sequences, respec tively, and organization of the six exons comprising the gene is simil ar to the human gene. Northern analysis and in situ hybridization reve aled that MAT is expressed in the normal cycling, pregnant, and postpa rtum uterus, with levels of expression highest in the involuting uteru s at early time points (6 h to 1.5 days postpartum). The mRNA was conf ined to epithelial cells lining the lumen and some glandular structure s. High constitutive levels of MAT transcripts were also detected in t he small intestine, where expression was localized to the epithelial P aneth cells at the base of the crypts. Similarly, MAT expression was f ound in epithelial cells of the efferent ducts, in the initial segment and cauda of the epididymis, and in an extra-hepatic branch of the bi le duct. MAT transcripts were detectable only by reverse transcription -polymerase chain reaction in the colon, kidney, lung, skeletal muscle , skin, stomach, juvenile uterus, and normal, lactating, and involutin g mammary gland, as was expression primarily late in embryogenesis. An alysis of MAT expression during postnatal development indicated that a lthough MAT is expressed in the juvenile small intestine and reproduct ive organs, the accumulation of significant levels of MAT mRNA appears to correlate with organ maturation. These results show that MAT expre ssion is restricted to specific organs in the mouse, where the mRNA is produced exclusively by epithelial cells, and suggest that in additio n to matrix degradation and remodeling, MAT may play an important role in the differentiated function of these organs.