title: Matrix metalloproteinase gene polymorphisms and bronchopulmonary dysplasia: identification of MMP16 as a new player in lung development.
abstract: 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).
  
  
  RESULTS
  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 and MMP16 genes. 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 may 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.
authors.affiliation: INSERM, Unité 841, IMRB, équipe 06, Créteil, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Hadchouel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Decobert
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Franco-Montoya
authors.forename: Isabelle
authors.initials: I
authors.lastname: Halphen
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Jarreau
authors.forename: Olivier
authors.initials: O
authors.lastname: Boucherat
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Martin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.forename: Jacques
authors.initials: J
authors.lastname: Bourbon
authors.forename: Claude
authors.initials: C
authors.lastname: Danan
authors.forename: Christophe
authors.initials: C
authors.lastname: Delacourt
mesh_terms: D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000201:enzymology* / Q000254:growth & development*; D008297:Male; D053513:Matrix Metalloproteinase 16 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000494:pharmacology; D014132:Trachea / Q000201:enzymology / Q000254:growth & development
chemical_list: D013501:Surface-Active Agents; D053513:Matrix Metalloproteinase 16
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