S'abonner

068 - Matrix metalloproteinase gene polymorphisms and bronchopulmonary dysplasia: identification of MMP16 as a new player in lung development - 05/12/08

Doi : RMR-11-2008-25-9-0761-8425-101019-200810933 

A. Hadchouel [1 et 2],

F. Decobert [1, 2 et 3],

ML. Franco-Montoya [1 et 2],

P. Jarreau [2 et 4],

C. Danan [1, 2, 3 et 5],

J.  Bourbon [1 et 2],

C. Delacourt [1 et 2]

Voir les affiliations

Bienvenue sur EM-consulte, la référence des professionnels de santé.
Article gratuit.

Connectez-vous pour en bénéficier!

Background: Alveolarization requires coordinated extracellular matrix remodeling, a process in which matrix metalloproteinases (MMPs) play an important role. We postulated that polymorphisms in MMP genes might affect MMP function in preterm lungs, and thus influence the risk of bronchopulmonary dysplasia (BPD).

Methods: Two hundred and eighty-four consecutive neonates with a gestational age of < 28 weeks were included in this prospective study. Forty-five neonates developed BPD. Nine single-nucleotide polymorphisms (SNPs) were sought in the MMP2, MMP14 (or membrane-type one MMP, MT1-MMP) and MMP16 (or MT3- MMP) genes.

Results: After adjustment for birth weight and ethnic origin, the TT genotype of MMP16 C/T (rs2664352) and the GG genotype of MMP16 A/G (rs2664349) were found to protect from BPD. These genotypes were also associated with a smaller active fraction of MMP2 and with a 3-fold-lower MMP16 protein level in tracheal aspirates collected within 3 days after birth. Further evaluation of MMP16 expression during the course of normal human and rat lung development showed relatively low expression during the canalicular and saccular stages and a clear increase in both mRNA and protein levels during the alveolar stage. In two newborn rat models of arrested alveolarization, the lung MMP16 mRNA level was less than 50% of normal.

Conclusions: MMP16 appears to be involved in the development of lung alveoli. MMP16 polymorphisms appear to influence not only the pulmonary expression and function of MMP16 but also the risk of BPD in premature infants.




© 2008 Elsevier Masson SAS. Tous droits réservés.
Imprimer
Export

    Export citations

  • Fichier

  • Contenu

Vol 25 - N° 9

P. 1190 - novembre 2008 Retour au numéro
Article précédent Article précédent
  • 067 - Identification and characterization of two new TTF-1 mutations associated with pediatric interstitial lung diseases
  • L. Guillot, A. Carre, G. Szinnai, E. Tron, M. Castanet, D. Feldmann, A. Clement, M. Polak, R. Epaud
| Article suivant Article suivant
  • 069 - Role of cytosolic phospholipase A2 in Pseudomonas aeruginosa- induced inflammation
  • Y. Wu, D. Leduc, I. Garcia-Verdugo, V. Balloy, M. Chignard, L. Touqui