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 family of matrix metalloproteinases (MMPs) because of its exclusive pattern 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 collagenase 2. The isolated cDNA contains an open reading frame coding for a polypeptide of 465 amino acids, which is 74% identical to its human counterpart. The mouse collagenase 2 exhibits the domain structure characteristic of several MMPs, including a signal sequence, a prodomain with the cysteine residue essential for enzyme latency, an activation locus with the Zinc-binding site, and a COOH-terminal fragment with sequence similarity to hemopexin. It also contains the three conserved residues (Tyr-209, Asp-230, and Gly-232) located around the Zinc-binding site and are distinctive of the collagenase subfamily. Northern blot analysis of RNAs isolated from a variety of mouse tissues revealed that collagenase 2 is expressed at late stages during mouse embryogenesis, coinciding with the appearance of hematopoietic cells. In addition, collagenase 2 was highly expressed in the postpartum uterus starting 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 generation of the collagenolytic activity required during the process of massive connective tissue resumption occurring in the involuting uterus.
Balbín
M
M
Departamento, Facultad de Medicina, Universidad de Oviedo, Oviedo 33006, Spain.
Fueyo
A
A
Knäuper
V
V
Pendás
A M
AM
López
J M
JM
Jiménez
M G
MG
Murphy
G
G
López-Otín
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics*; D017124:Conserved Sequence; D004971:Estrus; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D020784:Matrix Metalloproteinase 8; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology; D010053:Ovary / Q000201:enzymology; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014599:Uterus / Q000201:enzymology / Q000502:physiology*
D017364:Collagenases; D020784:Matrix Metalloproteinase 8