The distribution of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the lungs of congenital diaphragmatic hernia patients and age-matched controls.
OBJECTIVE
In congenital diaphragmatic hernia (CDH), the pathogenesis of abnormal pulmonary morphology is still incompletely understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are known to play an important role in the turnover of the extracellular matrix (ECM) during development and in remodelling of tissue. The aim of this study was to investigate differences in the expression of MMPs and TIMPs between CDH lungs and controls, against the background of the abnormal pulmonary vasculature in CDH.


METHODS
We studied 12 lungs of term CDH patients who died < 24 h after birth and 11 normal age-matched control lungs, by immunohistochemistry with antibodies against human MMP-1, -2, -9, TIMP-1 and -2.


RESULTS
There was a clear increase in the number of MMP-1-reactive capillaries and fibroblasts in CDH lungs compared with controls. In contrast, TIMP-2 reactivity in these structures was decreased in CDH lungs. The arterial endothelium and medial smooth muscle expressed MMP-2, -9 and TIMP-2 in both CDH and control lungs. In small arteries (< 100 microm in diameter), the positive surface area of MMP-2, -9 and TIMP-2 was significantly larger in CDH lungs than in controls. There was no difference in the distribution and expression of TIMP-1 between CDH lungs and normal controls.


CONCLUSIONS
The differences in staining pattern of MMPs and TIMPs between normal and CDH lungs suggest that these enzymes might play a role in the abnormal remodelling of the interstitium and the pulmonary arteries in CDH lungs. This could contribute to our understanding of the abnormal lung morphology and the occurrence of pulmonary hypertension, which forms one of the major obstacles to the successful treatment of these patients.
Masumoto
K
K
Department of Paediatric Surgery, Erasmus MC-Sophia, Rotterdam, the Netherlands.
de Rooij
J D
JD
Suita
S
S
Rottier
R
R
Tibboel
D
D
de Krijger
R R
RR
D005865:Gestational Age; D006548:Hernia, Diaphragmatic / Q000378:metabolism / Q000473:pathology*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1