EXPRESSION AND ACTIVITY OF MATRIX METALLO PROTEINASES 2 AND 9 AND THEIR INHIBITORS IN RAT LUNGS DURING THE PERINATAL PERIOD AND IN DIAPHRAGMATIC HERNIA

Abstract

During lung development, the extracellular matrix undergoes dynamic remodeling. Matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs), are important enzymes that participate in regulating tissue remodeling. There is an abnormal balance of the synthesis and degradation of collagen and elastin in perinatal lung associated with congenital diaphragmatic hernia (CDH). This study was designed to (1) determine the expression and gelatinolytic activity patterns of MMPs 2 and 9 and TIMPs 1 and 2 in rat lungs during the perinatal period, and (2) to test the hypothesis that they are abnormal in nitrofen-induced CDH. Measurements were made using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and zymography. The mRNA expression and activity of MMP 2 did not change significantly from embryonic day 16 to postnatal day 14. The most striking feature found was the rapid increase in the expression of MMP 9 soon after birth. Measurements were repeated on lung tissue isolated from embryonic rats with nitrofen-induced CDH. The expression and activity of MMPs and TIMPs were similar to control values and thus we conclude that these proteins appear not to be responsible for the altered extracellular matrix and morphological abnormalities noted in CDH lungs at birth.