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.

MMP-2 and MMP-9 and Their Tissue Inhibitors in the Plasma of Preterm and Term Neonates

“…This is consistent with the observation by Lemke et al (17). The postnatal growth and development of organs such as kidney, brain and lung takes months and years.…”

The distribution of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the lungs of congenital diaphragmatic hernia patients and age‐matched controls

“…In this study, no differences in MMP‐1 or TIMP‐1 expression were found in the arterial vessel wall between normal and CDH lungs, despite the increase in type I collagen that has been described in the latter. This finding is in agreement with a previous study on CDH lungs from the nitrofen rat model, which analysed TIMP‐1 by Western blotting, reverse transcriptase‐polymerase chain reaction and zymography 22 . In the experimental rat model of pulmonary hypertension, which has thick arterial walls, an increase in MMP‐1 and TIMP‐1 activity has been shown in the arterial wall 23 .…”

“…However, Lemke et al . did not find any differences of MMP‐2, ‐9, TIMP‐1 or ‐2 by various methods 22 . In our study, the expression of MMP‐1 was higher and that of TIMP‐2 was lower in the interstitium of CDH lungs as opposed to controls.…”

Pulmonary elastin expression is decreased in the nitrofen-induced rat model of congenital diaphragmatic hernia

“…[29][30][31] It does not appear that matrix metalloproteinases or tissue inhibitors of metalloproteinases alter the expression of elastin in the nitrofen CDH rat lung. 32 Decreased elastin expression in CDH lungs may be caused by altered mechanical factors. Normal lung growth in utero requires mechanical distension of the lungs associated with fetal breathing movements and lung secretions.…”