Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Doi, T; Ruttenstock, E; Dingemann, J; Puri, P.
Spatiotemporal alteration in phosphatidylinositide 3-kinase-serine/threonine protein kinase B signaling in the nitrofen-induced hypoplastic lung.
J Pediatr Surg. 2010; 45(2):366-371 Doi: 10.1016/j.jpedsurg.2009.10.075
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Ruttenstock Elke Maria
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Purpose: The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is not fully understood. The serine/threonine protein kinase B (AKT) plays important roles for lung morphogenesis through epithelial-mesenchymal interaction in phosphatidylinositide 3-kinase (PI3K)-dependent manner. It has been reported that the lung explant morphogenesis in mice is interfered by inhibitors of the PI3K-AKT pathway. We hypothesized that PI3K and AKT gene and protein expression/distribution are altered during epithelial morphogenesis in the nitrofen-induced hypoplastic lung. Methods: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups as follows: control, nitrofen with CDH (CDH[-]), and nitrofen without CDH (CDH[+]) (n = 8 at each time-point, respectively). Reverse transcription polymerase chain reaction and immunohistochemistry were performed. Results: Messenger RNA expression levels of PI3K at D21 was significantly decreased in CDH(-) and CDH(+) group (5.71 +/- 0.85 and 6.80 +/- 0.88, respectively) compared to controls ( 8.95 +/- 3.22; P < .05). Messenger RNA levels of AKT were also significantly decreased at D18 in CDH(-) and CDH(+) lungs (1.21 +/- 0.16 and 1.20 +/- 0.32, respectively) compared to controls (1.62 +/- 0.14; P < .01). The PI3K immunoreactivity was diminished in the distal epithelium at D18 and decreased in the overall intensity at D21 in hypoplastic lungs compared to controls. The AKT immunoreactivity was decreased in mesenchyme at D18 and decreased overall intensity at D21 in CDH lungs compared to controls. Conclusion: Spatiotemporal alteration of pulmonary PI3K and AKT gene and protein expression during epithelial morphogenesis may interfere with epithelial-mesenchymal interaction, causing pulmonary hypoplasia in CDH by disrupting PI3K-AKT signaling pathway. (C) 2010 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Disease Models, Animal -; Down-Regulation - genetics; Female -; Fetal Diseases - genetics Fetal Diseases - metabolism; Fetal Organ Maturity - genetics; Functional Laterality -; Gene Expression Regulation, Developmental -; Gestational Age -; Hernia, Diaphragmatic - chemically induced Hernia, Diaphragmatic - congenital Hernia, Diaphragmatic - metabolism; Immunohistochemistry -; Lung - abnormalities Lung - embryology Lung - metabolism; Mice -; Morphogenesis - genetics; Phenyl Ethers -; Pregnancy -; Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism; Rats -; Rats, Sprague-Dawley -; Reverse Transcriptase Polymerase Chain Reaction -; Signal Transduction - genetics Signal Transduction - physiology; Transcription Factors - genetics Transcription Factors - metabolism
Find related publications in this database (Keywords): PI3K; AKT; Nitrofen; Hypoplastic lung; Congenital diaphragmatic hernia