Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Friedmacher, F; Hofmann, AD; Takahashi, H; Takahashi, T; Gosemann, JH; Puri, P.
Disruption of THY-1 signaling in alveolar lipofibroblasts in experimentally induced congenital diaphragmatic hernia.
Pediatr Surg Int. 2014; 30(2):129-135
Doi: 10.1007/s00383-013-3444-z
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Friedmacher Florian
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- Abstract:
- Pulmonary hypoplasia (PH), characterized by alveolar immaturity, remains the main cause of neonatal mortality and long-term morbidity in infants with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) are critically important for normal alveolar development. Thymocyte antigen 1 (Thy-1) is a highly expressed cell-surface protein in this specific subset of lung fibroblasts, which plays a key role in fetal alveolarization by coordinating the differentiation and lipid homeostasis of alveolar LIFs. Thy-1 increases the lipid content of LIFs by upregulation of adipocyte differentiation-related protein (ADRP), a lipogenic molecular marker characterizing pulmonary LIFs. Thy-1 (-/-) mice further show impaired alveolar development with reduced proliferation of pulmonary LIFs, resulting in a PH-similar phenotype. We hypothesized that pulmonary Thy-1 signaling is disrupted in experimentally induced CDH, which may has an adverse effect on the lipid content of alveolar LIFs. Timed-pregnant Sprague-Dawley rats were treated with either 100 mg nitrofen or vehicle on embryonic day 9.5 (E9.5). Fetuses were killed on E21.5, and lungs were divided into controls (n = 14) and CDH-associated PH (n = 14). Pulmonary gene expression levels of Thy-1 and ADRP were assessed by quantitative real-time PCR. ADRP immunohistochemistry and oil-red-O staining were used to localize alveolar LIF expression and lipid droplets. Immunofluorescence double staining for Thy-1 and oil-red-O was performed to evaluate Thy-1 expression and lipid content in alveolar LIFs. Radial alveolar count was significantly reduced in CDH-associated PH with significant downregulation of pulmonary Thy-1 and ADRP mRNA expression compared to controls. ADRP immunoreactivity and lipid droplets were markedly diminished in alveolar interstitial cells, which coincided with decreased alveolar LIF expression in CDH-associated PH compared to controls. Confocal laser scanning microscopy confirmed markedly decreased Thy-1 expression and lipid content in alveolar LIFs of CDH-associated PH compared to controls. Our study provides strong evidence that disruption of pulmonary Thy-1 signaling results in reduced lipid droplets in alveolar LIFs and may thus contribute to PH in the nitrofen-induced CDH model. Treatment modalities aimed at increasing lipid content in alveolar LIFs may therefore have a therapeutic potential in attenuating CDH-associated PH.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Disease Models, Animal -
- Female -
- Fibroblasts - metabolism
- Gene Expression - genetics
- Hernia, Diaphragmatic - embryology
- Hernia, Diaphragmatic - genetics
- Hernia, Diaphragmatic - metabolism
- Hernias, Diaphragmatic, Congenital -
- Mice -
- Pregnancy -
- Pulmonary Alveoli - embryology
- Pulmonary Alveoli - metabolism
- Rats -
- Rats, Sprague-Dawley -
- Signal Transduction - genetics
- Thy-1 Antigens - genetics
- Up-Regulation -
- Find related publications in this database (Keywords)
- Thymocyte antigen 1
- Adipocyte differentiation-related protein
- Alveolar lipofibroblast
- Pulmonary hypoplasia
- Congenital diaphragmatic hernia