Description
Matrix metalloproteinase-7 (MMP-7) also known as matrilysin and PUMP (EC 3.4.24.23) cleaves a number of substrates including collagen types IV and X, elastin, fibronectin, gelatin, laminin and proteoglycans. MMP-7 is closely related to the stromelysin family members but is encoded by a different gene. MMP-7 is the smallest of all the MMPs consisting of a pro-peptide domain and a catalytic domain. It lacks the hemopexin-like domain common to other members of the MMPs. MMP-7 is secreted as a 28kD proenzyme and can be activated in vitro by organomercurials and trypsin and in vivo by MMP-3 to a 18kD active MMP-7 enzyme. Once activated, MMP-7 can activate pro-MMP-1 and pro-MMP-9 but not pro-MMP-2. MMP-7 is widely expressed having been reported in elevated levels in cycling endometrium as well as in colorectal cancers and adenomas, hepatocellular carcinomas, rectal carcinomas, and approximately 50% of gliomas.
Defensins are a large family of broad-spectrum antimicrobial peptides, identified originally in leukocytes of rabbits and humans. The genes encoding human a and ß -defensins are clustered in a contiguous segment of chromosome 8p23. Defensins are classified into two families designated a-and ß-based on distinctive, although similar, tri-disulfide linkages in the peptides. b-defensins are slightly larger and differ in the position and arrangement of 3 disulfides. In humans, six a -defensin (cryptidins), HD 1-6 (HD1-4 are also known as HNP1-4 for Human Neutrophil Peptides), and two ß -defensins, HBD-1 and HBD-2, have been identified to date. Rat (RBD-1 and RBD-2) and mouse (MBD1-4) homologues of the human beta-defensin have also been identified.
Defensins are initially synthesized as inactive prodefensins with a signal peptide that is cleaved off by Matrilysin/MMP7 (a tissue metalloproteinase) to generate mature and bioactive defensin peptide. Matrilysin is expressed in Paneth cell granules together with perhaps more than 20 different a-defensins (cryptidins). Disruption of the matrilysin gene prevents the normal posttranslational proteolytic activation of intestinal a-prodefensins