COLLAGENASE-2 (MMP-8) EXPRESSION IN MURINE TISSUE-REMODELING PROCESSES - ANALYSIS OF ITS POTENTIAL ROLE IN POSTPARTUM INVOLUTION OF THE UTERUS

Neutrophil collagenase or collagenase 2 (MMP-8) is unique among the fa mily of matrix metalloproteinases (MMPs) because of its exclusive patt ern of expression in inflammatory conditions. At present, no evidence of the occurrence of this enzyme in tissues other than human has been reported. In this work, we have cloned the murine homologue of human c ollagenase 2. The isolated cDNA contains an open reading frame coding for a polypeptide of 465 amino acids, which is 74% identical to its hu man counterpart. The mouse collagenase 2 exhibits the domain structure characteristic of several MMPs, including a signal sequence, a prodom ain with the cysteine residue essential for enzyme latency, an activat ion locus with the Zinc-binding site, and a COOH-terminal fragment wit h sequence similarity to hemopexin. It also contains the three conserv ed residues (Tyr-209, Asp-230, and Gly-232) located around the Zinc-bi nding site and are distinctive of the collagenase subfamily. Northern blot analysis of RNAs isolated from a variety of mouse tissues reveale d that collagenase 2 is expressed at late stages during mouse embryoge nesis, coinciding with the appearance of hematopoietic cells. In addit ion, collagenase 2 was highly expressed in the postpartum uterus start ing at 1 day postpartum and extending up to 5 days. Enzymatic analysis revealed that matrilysin, another MMP overexpressed in uterine tissue , is able to activate murine procollagenase 2. These data suggest that both enzymes could form an activation cascade resulting in the genera tion of the collagenolytic activity required during the process of mas sive connective tissue resumption occurring in the involuting uterus.