« Previous AbstractFibrillin-1 Expression Is Decreased in the Diaphragmatic Muscle Connective Tissue of Nitrofen-Induced Congenital Diaphragmatic Hernia    Next AbstractGata-6 expression is decreased in diaphragmatic and pulmonary mesenchyme of fetal rats with nitrofen-induced congenital diaphragmatic hernia »

Eur J Pediatr Surg

Title:		"Decreased Expression of Integrin Subunits alpha3, alpha6, and alpha8 in the Branching Airway Mesenchyme of Nitrofen-Induced Hypoplastic Lungs"
Author(s):		Takahashi T; Friedmacher F; Zimmer J; Puri P;
Address:		"National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. Department of Pediatric Surgery, Medizinische Hochschule Hannover Zentrum Chirurgie, Hannover, Germany"
Journal Title:		Eur J Pediatr Surg
Year:		2018
Volume:		20170712
Issue:		1
Page Number:		109 - 114
DOI:		10.1055/s-0037-1604022
ISSN/ISBN:		1439-359X (Electronic) 0939-7248 (Linking)
Abstract:		"INTRODUCTION: Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major cause of neonatal mortality in newborns with congenital diaphragmatic hernia (CDH). Integrin-mediated cell-matrix interactions play an essential role in the fetal lung mesenchyme by stimulating branching morphogenesis. Mice lacking integrin subunits alpha3 (Itga3) and alpha6 (Itga6) exhibit severe PH. Furthermore, Itga8-knockout mice show defective airway branching, suggesting that Itga3, Itga6, and Itga8 are crucial for fetal lung development. We hypothesized that expression of Itga3, Itga6, and Itga8 is decreased in the branching airway mesenchyme of hypoplastic rat lungs in the nitrofen-induced CDH model. MATERIALS AND METHODS: Time-mated rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D15, D18, and D21, and dissected lungs were divided into control and nitrofen-exposed specimens (n = 12 per time-point and group, respectively). Pulmonary gene expression of Itga3, Itga6, and Itga8 was analyzed by quantitative real-time polymerase chain reaction. Immunofluorescence double-staining for Itga3, Itga6, and Itga8 was combined with the mesenchymal marker Fgf10 to evaluate protein expression and localization in branching airway tissue. RESULTS: Relative mRNA expression of Itga3, Itga6, and Itga8 was significantly decreased in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Itga3, Itga6, and Itga8 mainly in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. CONCLUSION: Decreased expression of Itga3, Itga6, and Itga8 in the pulmonary mesenchyme may lead to disruptions in airway branching morphogenesis, thus contributing to PH in the nitrofen-induced CDH model"
Keywords:		"Abnormalities, Multiple/chemically induced/embryology/*metabolism Animals Biomarkers/metabolism Fluorescent Antibody Technique Hernias, Diaphragmatic, Congenital/chemically induced/*complications/embryology Integrin alpha Chains/*metabolism Integrin alpha;"
Notes:		"MedlineTakahashi, Toshiaki Friedmacher, Florian Zimmer, Julia Puri, Prem eng 2017/07/13 Eur J Pediatr Surg. 2018 Feb; 28(1):109-114. doi: 10.1055/s-0037-1604022. Epub 2017 Jul 12"