Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Thangaratnarajah, C; Dinger, K; Vohlen, C; Klaudt, C; Nawabi, J; Lopez Garcia, E; Kwapiszewska, G; Dobner, J; Nüsken, KD; van Koningsbruggen-Rietschel, S; von Hörsten, S; Dötsch, J; Alejandre Alcázar, MA.
Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction.
Am J Physiol Lung Cell Mol Physiol. 2017; 313(3):L491-L506
Doi: 10.1152/ajplung.00432.2016
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- Co-Autor*innen der Med Uni Graz
- Kwapiszewska-Marsh Grazyna
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- Abstract:
- Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, we showed in our previous studies that altered lung structure is related to IL-6/STAT3 signaling. As neuropeptide Y (NPY), a coneurotransmitter of the sympathetic nervous system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Finally, primary neonatal lung myofibroblasts (pnF) and murine embryonic fibroblasts (MEF) were used to assess proliferation, apoptosis, migration, and IL-6 expression. At E21, NPY and IL-6 expression was decreased, and AKT/PKC and STAT3/AMPKα signaling was reduced. Early reduction of NPY/IL-6 was associated with increased chord length in lungs after IUGR at P3, indicating reduced alveolar formation. At P23, however, IUGR rats exhibited a catch-up of body weight and alveolar growth coupled with more proliferating myofibroblasts. These structural findings after IUGR were linked to activated NPY/PKC, IL-6/AMPKα signaling. Complementary, IUGR-pnF showed increased survival, impaired migration, and reduced IL-6 compared with control-pnF (Co-pnF). In contrast, NPY induced proliferation, migration, and increased IL-6 synthesis in fibroblasts. Additionally, NPY-/- mice showed reduced IL-6 signaling and less proliferation of lung fibroblasts. Our study presents a novel role of NPY during alveolarization: NPY regulates 1) IL-6 and lung STAT3/AMPKα signaling, and 2) proliferation and migration of myofibroblasts. These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth. Copyright © 2017 the American Physiological Society.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenylate Kinase - metabolism
- Animals -
- Animals, Newborn -
- Apoptosis - genetics
- Biomarkers - metabolism
- Cell Movement - genetics
- Cell Proliferation - genetics
- Cell Survival - genetics
- Diet -
- Fetal Growth Retardation - immunology
- Fetal Growth Retardation - pathology
- Gene Expression Regulation -
- Interleukin-6 - genetics
- Interleukin-6 - metabolism
- Lung - growth & development
- Lung - pathology
- Mice, Inbred C57BL -
- Mice, Knockout -
- Models, Biological -
- Myofibroblasts - metabolism
- Neuropeptide Y - metabolism
- Neurotransmitter Agents - metabolism
- Protein Kinase C - metabolism
- Rats, Wistar -
- Receptors, Neuropeptide Y - metabolism
- STAT3 Transcription Factor - metabolism
- Signal Transduction - genetics
- Suppressor of Cytokine Signaling 3 Protein - metabolism
- Sympathetic Nervous System - immunology
- Sympathetic Nervous System - pathology
- Weight Gain -
- Find related publications in this database (Keywords)
- neuropeptide Y
- neuroimmune interaction
- neonatal lung myofibroblasts
- alveolarization
- intrauterine growth restriction
- neonatal chronic lung disease