Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Friedmacher, F; Fujiwara, N; Hofmann, AD; Takahashi, H; Alvarez, LA; Gosemann, JH; Puri, P.
Prenatal retinoic acid increases lipofibroblast expression in hypoplastic rat lungs with experimental congenital diaphragmatic hernia.
J Pediatr Surg. 2014; 49(6):876-881
Doi: 10.1016/j.jpedsurg.2014.01.017
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Friedmacher Florian
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- Abstract:
- Prenatal administration of all-trans retinoic acid (ATRA) has been shown to stimulate alveolarization in nitrofen-induced pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial lipofibroblasts (LIFs), characterized by adipocyte differentiation-related protein (ADRP), play a critical role in alveolar development by coordinating lipid homeostasis. Previous studies have demonstrated that ATRA positively affects LIF expression in developing lungs. We hypothesized that pulmonary LIF expression is increased after prenatal ATRA treatment in the nitrofen model of CDH-associated PH. Timed-pregnant rats were treated with nitrofen or vehicle on E9.5, followed by injection of ATRA or placebo on E18.5, E19.5, and E20.5. Fetal lungs were dissected on E21.5 and divided into Control+Placebo, Control+ATRA, Nitrofen+Placebo, and Nitrofen+ATRA. Pulmonary gene expression levels of ADRP were analyzed by quantitative real-time polymerase chain reaction, and LIF expression was investigated by ADRP immunohistochemistry, oil-red-O-, and immunofluorescence-double-staining. Relative mRNA expression of pulmonary ADRP was significantly increased in Nitrofen+ATRA compared to Nitrofen+Placebo (0.31±0.02 vs. 0.08±0.01; P<0.0001). ADRP immunoreactivity and oil-red-O-staining were markedly increased in alveolar interstitium of Nitrofen+ATRA compared to Nitrofen+Placebo. Immunofluorescence-double-staining confirmed markedly increased LIF expression in alveolar walls of Nitrofen+ATRA compared to Nitrofen+Placebo. Increased LIF expression after prenatal treatment with ATRA in nitrofen-induced PH suggests that ATRA may have a therapeutic potential in attenuating CDH-associated PH by stimulating alveolar development. Copyright © 2014 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Differentiation -
- Female -
- Fibroblasts - drug effects
- Fibroblasts - metabolism
- Fibroblasts - pathology
- Gene Expression Regulation, Developmental - drug effects
- Hernias, Diaphragmatic, Congenital - drug therapy
- Hernias, Diaphragmatic, Congenital - genetics
- Hernias, Diaphragmatic, Congenital - metabolism
- Immunohistochemistry -
- Lung - abnormalities
- Lung - metabolism
- Membrane Proteins - biosynthesis
- Membrane Proteins - genetics
- Organogenesis - drug effects
- Perilipin-2 -
- Phenyl Ethers - toxicity
- Pregnancy -
- Pregnancy, Animal -
- RNA, Messenger - genetics
- Rats -
- Rats, Sprague-Dawley -
- Real-Time Polymerase Chain Reaction -
- Reverse Transcriptase Polymerase Chain Reaction -
- Tretinoin - pharmacology
- Up-Regulation -
- Find related publications in this database (Keywords)
- Retinoic acid
- Lipofibroblast
- Adipocyte differentiation-related protein
- Pulmonary hypoplasia
- Congenital diaphragmatic hernia