Novel functional role of GH/IGF1 axis in neonatal lung fibroblasts is linked to lung growth after intrauterine growth restriction
| Autor: | Katharina Dinger, Jawed Nawabi, Jörg Dötsch, Christina Vohlen, Celien Kuiper, Eva Lopez Garcia, Chansutha Thangaratnarajah, Kai-D. Nüsken, Silke van Koningsbruggen-Rietschel, Miguel A. Alejandre Alcazar, Christian Klaudt |
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| Rok vydání: | 2017 |
| Předmět: |
endocrine system
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Lung biology business.industry Growth factor medicine.medical_treatment Intrauterine growth restriction medicine.disease female genital diseases and pregnancy complications medicine.anatomical_structure Endocrinology Bronchopulmonary dysplasia Fibrosis Cord blood Internal medicine embryonic structures medicine biology.protein business Protein kinase B Elastin reproductive and urinary physiology |
| Zdroj: | Lung and Airway Developmental Biology. |
| Popis: | Background: Intrauterine growth restriction (IUGR) is a risk factor for bronchopulmonary dysplasia, characterized by reduced alveoli and fibrosis. Prior studies of our group showed fibrosis in rat lungs after IUGR. Growth Hormone (GH) and Insulin-like growth factor 1 (IGF1) are important in development and dysregulated in cord blood of infants with IUGR. Aims: To investigate if (1) lung growth after IUGR is related to dysregulated lung GH/IGF1 signaling; and if (2) GH/IGF1 signaling is linked to neonatal lung fibroblast function. Methods: (1) IUGR in Wistar rats was induced by isocaloric low protein diet during gestation. Lungs were obtained on embryonic day (E)21, postnatal day (P)3, and P23. (2) Cell culture: primary neonatal rat fibroblasts (PnF) were isolated from lungs of Control (Co-PnF) and IUGR (IUGR-PnF). Results: (1) E21: Lung GH mRNA was increased, GH-Receptor (GH-R) protein and Stat5 signaling were reduced; and lung IGF1 mRNA and IGF1-R signaling (Akt) were decreased in IUGR lungs. P23: increment of GH-R/IGF1-R protein was linked to active Akt and Stat5 in lungs after IUGR. Increased septal thickness after IUGR was related to higher PCNA/CyclinD1 protein (proliferation) and col1α1, elastin and αSMA mRNA. Serum IGF1, however, was reduced after IUGR. (2) GH/pStat5 signaling, PCNA and CyclinD1 protein were increased in IUGR-PnF. Both GH and IGF1 induced proliferation and migration of Control-PnF; only IGF1 had these effects on IUGR-PnF. Conclusion: Thus, we show a potential novel mechanism by which GH/IGF1 axis in lung fibroblasts could account for lung growth after IUGR. Those new insights offer potential new strategies to enable lung growth. |
| Databáze: | OpenAIRE |
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