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Ruttenstock, EM; Doi, T; Dingemann, J; Puri, P.
Prenatal retinoic acid upregulates connexin 43 (Cx43) gene expression in pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia rat model.
J Pediatr Surg. 2012; 47(2): 336-340.
Doi: 10.1016/j.jpedsurg.2011.11.026
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Ruttenstock Elke Maria
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- Abstract:
- Purpose: Connexin 43 (Cx43), a major gap junction protein, is necessary for alveologenesis and plays an important role in the differentiation of type II to type I alveolar epithelial cells. Knockout mice of Cx43 display severe pulmonary hypoplasia (PH). Prenatal administration of retinoic acid (RA) is known to stimulate alveologenesis in nitrofen-induced PH. Recent studies revealed that retinoids upregulate Cx43 expression. We hypothesized that gene expression of Cx43 is downregulated during alveologenesis and that administration of RA upregulates Cx43 expression in the nitrofen-induced PH. Methods: Pregnant rats were exposed to olive oil or nitrofen on day 9 (D9) of gestation. Retinoic acid was given intraperitoneally on D18, D19, and D20. Fetal lungs were harvested on D18 and D21 and divided into control, nitrofen, control+RA (D21), and nitrofen+RA (D21). The Cx43 expression levels were determined using reverse transcription polymerase chain reaction and immunohistochemistry. Results: On D18 and D21, Cx43 relative messenger RNA expression levels were significantly downregulated in nitrofen compared with those in the control group. On D21, expression levels of Cx43 were significantly upregulated in nitrofen+RA and control+RA compared with those in nitrofen group. Immunohistochemical studies confirmed these results. Conclusion: Downregulation of Cx43 expression may interfere with normal alveologenesis. Upregulation of Cx43 pulmonary gene expression after RA treatment may promote lung growth by stimulating alveologenesis in nitrofen-induced PH. (C) 2012 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Differentiation - drug effects
- Connexin 43 - biosynthesis Connexin 43 - genetics
- Disease Models, Animal -
- Drug Evaluation, Preclinical -
- Epithelial Cells - drug effects
- Female -
- Fetal Therapies -
- Gene Expression Regulation, Developmental - drug effects
- Hernia, Diaphragmatic - chemically induced Hernia, Diaphragmatic - congenital Hernia, Diaphragmatic - embryology Hernia, Diaphragmatic - metabolism
- Injections, Intraperitoneal -
- Lung - embryology Lung - metabolism Lung - pathology
- Phenyl Ethers - toxicity
- Pregnancy -
- RNA, Messenger - biosynthesis
- Random Allocation -
- Rats -
- Rats, Sprague-Dawley -
- Real-Time Polymerase Chain Reaction -
- Respiratory Mucosa - cytology Respiratory Mucosa - embryology
- Reverse Transcriptase Polymerase Chain Reaction -
- Tretinoin - pharmacology Tretinoin - therapeutic use
- Up-Regulation - drug effects
- Find related publications in this database (Keywords)
- Retinoic acid
- Nitrofen
- Pulmonary hypoplasia
- Connexin 43
- Congenital diaphragmatic hernia