Expression of a progelatinase activator (MT1-MMP) in human fetal membranes.

PROBLEM

The finding of MMP-2 (which degrades type IV collagen) and TIMP-2 (the tissue inhibitor of MMP) in fetal membranes suggests the possibility of membrane self-destruction as an etiology of premature rupture of fetal membranes. MMP-2 is activated by a membrane-bound MMP (MT1-MMP). This study was undertaken to detect the presence of MT1-MMP in human fetal membranes.

METHOD OF STUDY

Fetal membranes were placed in an organ explant system and stimulated with lipopolysaccaride (LPS). MT1-MMP expression was studied in frozen tissues by reverse transcriptase (RT)-polymerase chain reaction (PCR) using primers designed in our laboratory. DNA sequence analysis was performed to verify the specificity of PCR products. In situ hybridization and immunocytochemistry were used to localize MT1-MMP mRNA and peptide, respectively.

RESULTS

RT-PCR data indicated the presence of mRNA for MT1-MMP in fetal membranes. Although PCR is not quantitative, no differences in mRNA band intensities were noticed after LPS stimulation. MT1-MMP expression was constitutive throughout the culture period. In situ hybridization demonstrated amnion, chorionic laeve, cytotrophoblast cells, and the cells in the reticular and spongy layer of the extracellular matrix as the origin of MT1-MMP mRNA and peptide.

CONCLUSIONS

This is the first study documenting the amniochorionic membrane as a source of MT1-MMP mRNA and peptide. Activation of progelatinase A requires the presence of this membrane-associated MMP. The finding of MT1-MMP in a tissue already known to produce MMP-2 and TIMP-2 documents the full system for activation and inhibition of this gelatinase. During infection, an imbalance in the expression of MT1-MMP, MMP-2 and TIMP-2 may constitute an endogenous pathway of membrane degradation.