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Reduced expression of aquaporin 5 water channel in nitrofen-induced hypoplastic lung with congenital diaphragmatic hernia rat model.

Abstract：

PURPOSE:Pulmonary hypoplasia remains the principal cause of high morbidity and mortality in patients with congenital diaphragmatic hernia (CDH). The precise mechanisms causing lung hypoplasia remains unclear. Aquaporins (AQPs) are reported to constitute a family of water channels that facilitate membrane water permeability in various tissues of animals. Aquaporin 5 has been reported to be an important marker expressed in type I alveolar epithelial cells in late gestation and mediates water transport across the human airway epithelium. We hypothesized that AQP5 is reduced in hypoplastic lungs and therefore designed this study to determine AQP5 expression in normal and hypoplastic lungs. METHODS:Fetal rat lungs of control (n=23) and nitrofen-treated (n=37) dams were harvested on embryonic day (E) 15, E17, E19, and E21. The expression of the AQP5 was analyzed in each lung by real-time reverse transcriptase-polymerase chain reaction. Immunohistochemical studies were performed to evaluate the protein expression level of AQP5. RESULTS:Aquaporin 5 messenger RNA levels on E21 were significantly reduced in lungs from the nitrofen with CDH group (11.8 +/- 2.3) compared with normal controls (23.5 +/- 11.8) and nitrofen without CDH group (26.9 +/- 13.0) (P < .05). Aquaporin 5 immunohistochemistry demonstrated AQP5 strongly expressed at the apical membrane of type I alveolar epithelial cells in the normal and nitrofen without CDH groups. By contrast, the AQP5-positive cells were markedly reduced in hypoplastic lungs in the nitrofen with CDH group. CONCLUSION:Our results show that the expression of AQP5 is down-regulated in hypoplastic lungs with CDH. Down-regulation of AQP5 may result in abnormal pulmonary fluid metabolism in perinatal period and may be one of the mechanisms disturbing the pulmonary development in late stage in the CDH model.

journal_name

J Pediatr Surg

journal_title

Journal of pediatric surgery

authors

Takayasu H,Nakazawa N,Montedonico S,Puri P

doi

10.1016/j.jpedsurg.2006.10.029

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

415-9

issue

eissn

0022-3468

issn

1531-5037

pii

S0022-3468(06)00780-9

journal_volume

pub_type

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Reduced expression of aquaporin 5 water channel in nitrofen-induced hypoplastic lung with congenital diaphragmatic hernia rat model.