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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jpedsurg.2006.10.029 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Validation and in silico function prediction of circtial1 as a novel marker of abnormal lung development in nitrofen-induced congenital diaphragmatic hernia (CDH).
Pediatr Surg Int
December 2024
Division of Pediatric Surgery, Department of Surgery, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, AE402-820 Sherbrook Street, Winnipeg, MB, R3A 1S1, Canada.
Purpose: Circular RNAs (circRNAs) are stable, non-coding RNAs with tissue- and developmental-specific expression making them suitable biomarkers for congenital anomalies. Current circRNA discovery pipelines have focused on human and mouse. We aim to bridge this gap by combining bioinformatics resources and used circtial1 as a model candidate in the nitrofen rat model of congenital diaphragmatic hernia (CDH).
View Article and Find Full Text PDFSex-specific differences in the severity of pulmonary hypoplasia in experimental congenital diaphragmatic hernia and implications for extracellular vesicle-based therapy.
Pediatr Surg Int
October 2024
Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Purpose: Amniotic fluid stem cell extracellular vesicles (AFSC-EVs) hold regenerative potential to treat hypoplastic lungs secondary to congenital diaphragmatic hernia (CDH). This study aims to investigate sex-specific differences in pulmonary hypoplasia severity and responses to AFSC-EV administration in an experimental CDH mouse model.
Methods: C57BL/6J dams were fed with nitrofen + bisdiamine (left-sided CDH) or olive oil only (control) at embryonic day (E) 8.
Toll-like receptors ligand immunomodulators for the treatment congenital diaphragmatic hernia.
Orphanet J Rare Dis
October 2024
Centro de Biología Molecular "Severo Ochoa", CSIC-UAM, Madrid, Spain.
Article Synopsis
- Congenital diaphragmatic hernia (CDH) is a rare condition affecting diaphragm development, leading to lung issues, with no established treatments available.
- Research analyzed the effects of specific Toll-like receptor (TLR) ligands on CDH in rat and mouse models, focusing on immune cell behavior and gene expression.
- Findings revealed that TLR2/4 ligands significantly improved CDH by promoting healing in fetuses without toxicity, enhancing lung development, and stimulating beneficial macrophage activity.
Comparative Transcriptome Analysis of Human and Mouse Canalicular Lungs in Fetal Diaphragmatic Hernia.
J Pediatr Surg
November 2024
Division of General Pediatric Surgery, Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. Electronic address:
Background: The nitrofen model of congenital diaphragmatic hernia (CDH) is widely used in translational research. However, the molecular pathways associated with pulmonary hypoplasia in this model compared to the human CDH phenotype have not been well described. The aim of this study was to investigate differentially expressed genes (DEG) and signaling pathways in early stage fetal lungs in mouse and human CDH.
View Article and Find Full Text PDFArticle Synopsis
- Congenital diaphragmatic hernia (CDH) is a serious condition in newborns with a low survival rate, making it crucial to find ways to predict severe cases before birth.
- This study discovered four specific microRNAs (miRNAs) in amniotic fluid-derived small extracellular vesicles that can help differentiate between good and poor prognosis in CDH cases, with two miRNAs showing particularly strong predictive abilities.
- The research also highlighted differences in miRNA profiles between CDH-affected lung tissues and control tissues, suggesting that miRNA levels could provide valuable insights into lung health and help improve prenatal care for CDH patients.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!