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Hofmann, AD; Friedmacher, F; Hunziker, M; Takahashi, H; Duess, JW; Gosemann, JH; Puri, P.
Upregulation of serotonin-receptor-2a and serotonin transporter expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.
J Pediatr Surg. 2014; 49(6): 871-874.
Doi: 10.1016/j.jpedsurg.2014.01.015
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Friedmacher Florian
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- Abstract:
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Congenital diaphragmatic hernia (CDH) is attributed to severe pulmonary hypoplasia and pulmonary hypertension (PH). PH is characterized by structural changes resulting in vascular remodeling. Serotonin, a potent vasoconstrictor, plays a central role in the development of PH. It exerts its constricting effects on the vessels via Serotonin receptor 2A (5-HT2A) and induces pulmonary smooth muscle cell proliferation via the serotonin transporter (5-HTT). This study was designed to investigate expressions of 5-HT2A and 5-HTT in the pulmonary vasculature of rats with nitrofen-induced CDH.
Rats were exposed to nitrofen or vehicle on D9. Fetuses were sacrificed on D21 and divided into nitrofen and control group (n=32). Pulmonary RNA was extracted and mRNA level of 5HT2A was determined by qRT-PCR. Protein expression of 5HT2A and 5-HTT was investigated by western blotting. Confocal immunofluorescence double-staining for 5-HT2A, 5-HTT, and alpha smooth muscle actin were performed.
Pulmonary 5-HT2A gene expression levels were significantly increased in nitrofen-induced CDH compared to controls. Western blotting and confocal microscopy confirmed increased pulmonary protein expression in CDH lungs compared to controls.
Increased gene and protein expression of 5HT2A and 5-HTT in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that 5HT2A and 5-HTT are important mediators of PH in nitrofen-induced CDH.
Copyright © 2014 Elsevier Inc. All rights reserved.
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Animals -
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Blotting, Western -
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Disease Models, Animal -
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Female -
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Gene Expression Regulation, Developmental -
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Hernias, Diaphragmatic, Congenital - embryology Hernias, Diaphragmatic, Congenital - genetics Hernias, Diaphragmatic, Congenital - metabolism
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Lung - abnormalities Lung - drug effects Lung - embryology
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Microscopy, Confocal -
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Phenyl Ethers - toxicity
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Pregnancy -
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Pregnancy, Animal -
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RNA, Messenger - genetics
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Rats -
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Rats, Sprague-Dawley -
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Receptor, Serotonin, 5-HT2A - biosynthesis Receptor, Serotonin, 5-HT2A - genetics
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Reverse Transcriptase Polymerase Chain Reaction -
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Serotonin Plasma Membrane Transport Proteins - biosynthesis Serotonin Plasma Membrane Transport Proteins - genetics
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Up-Regulation -
- Find related publications in this database (Keywords)
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Congenital diaphragmatic hernia
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Nitrofen
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Pulmonary hypertension
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Vascular remodeling
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Serotonin receptor 2A
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Serotonin transporter