Matrix metalloproteinase gene polymorphisms and bronchopulmonary dysplasia: identification of MMP16 as a new player in lung development.
Matrix metalloproteinase gene polymorphisms and bronchopulmonary dysplasia: identification of MMP16 as a new player in lung development.
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基质金属蛋白酶基因多态性和支气管肺发育不良：将MMP16鉴定为肺发育领域的新参与者。
DOI：
10.1371/journal.pone.0003188
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发表时间：
2008-09-11
期刊：
影响因子：
3.7
通讯作者：
Delacourt C
中科院分区：
文献类型：
--
作者：
Hadchouel A;Decobert F;Franco-Montoya ML;Halphen I;Jarreau PH;Boucherat O;Martin E;Benachi A;Amselem S;Bourbon J;Danan C;Delacourt C
肺泡化需要协调的细胞外基质重塑，在这个过程中，基质金属蛋白酶(MMPs)起着重要作用。我们推测，基质金属蛋白酶基因的多态可能影响早产儿肺中基质金属蛋白酶的功能，从而影响支气管肺发育不良(BPD)的风险。284名连续出生的胎龄为28周的新生儿被纳入这项前瞻性研究。45例新生儿发生BPD。在MMP2、MMP14和MMP16基因上发现了9个单核苷酸多态(SNPs)。在调整出生体重和民族因素后，发现MMP16C/T的TT基因(Rs2664352)和MMP16A/G的GG基因(Rs2664349)对BPD有保护作用。这些基因型还与出生后3天内收集的气管抽吸物中较小的MMP2活性部分和低3倍的MMP16蛋白水平有关。对正常人和大鼠肺发育过程中MMP16表达的进一步评估显示，MMP16在肺小管期和囊状期的表达相对较低，而在肺泡期的表达水平明显升高。在两种新生鼠肺泡化受阻模型中，肺组织MMP16mRNA水平低于正常水平的50%。MMP16可能参与了肺泡的发育。MMP16基因多态性不仅影响肺组织MMP16的表达和功能，而且可能影响早产儿发生BPD的风险。
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). 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. 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.
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影响因子：
4.8
作者：
TAKINO, T;SATO, H;SEIKI, M
通讯作者：
SEIKI, M
影响因子：
8
作者：
Kazzi, S Nadya J;Kim, U Olivia;Buhimschi, Irina
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Buhimschi, Irina
影响因子：
3.6
作者：
Schulz, CG;Sawicki, G;Cheung, PY
通讯作者：
Cheung, PY
影响因子：
4.6
作者：
Boucherat, Olivier;Franco-Montoya, Marie-Laure;Bourbon, Jacques R.
通讯作者：
Bourbon, Jacques R.
影响因子：
2.7
作者：
Oblander, SA;Zhou, ZJ;Apte, SS
通讯作者：
Apte, SS