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Alterations in the Expression of Profilin1/pVASP‐S157 and Cofilin1/pVASP‐S239 in Perinatal Inflammation/Neonatal Hyperoxia‐Induced Lung Injury
Author(s) -
Ali Mehboob,
Heyob Kathryn M,
Rogers Lynette K
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.982.6
Subject(s) - hyperoxia , bronchopulmonary dysplasia , western blot , actin , phosphorylation , lung , blot , inflammation , andrology , pathology , serine , actin cytoskeleton , biology , microbiology and biotechnology , immunofluorescence , medicine , cell , cytoskeleton , immunology , biochemistry , antibody , pregnancy , gestational age , gene , genetics
Cell proliferation and migration have been shown to be regulated by actin dynamics/cytoskeletal remodeling. Profilin1, cofilin1 and VASP (phosphorylated at serine‐157 (pVASP‐S157) or serine‐239 (pVASP‐S239)) are the major regulators of actin remodeling within the cell. Infants that develop Bronchopulmonary Dysplasia (BPD) exhibit decreased alveolarization resulting from altered cellular proliferation and migration during septal formation. Using our mouse model of BPD, we tested the hypothesis that changes in expression and cellular localization of profilin1, cofilin1 and phosphorylated VASP play a key role in decreases in secondary septal formation and thus alveolarization. Human lung autopsy tissues from infants that died with BPD or controls were assessed for total F‐actin content and expression of profilin1, colfilin1, and phosphorylated VASP by immunofluorescence. Lung tissues were obtained from our murine model of maternal LPS exposure followed by 7 days of 85% hyperoxia. Murine tissues were harvested at 7 days of life and lung homogenates were assessed for profilin1, colfilin1, and VASP phosphorylation by western blot. A significant decrease in F‐actin content, pVASP‐157, pVASP‐S239, and profilin1 and an increase in cofilin1 were observed in BPD tissues compared to controls. Western blots from lung tissue homogenates indicated increases in cofilin1, profilin1, and pVASP‐S239 but a decrease pVASP‐S157 at 7 days. In conclusion, we propose that these alterations in expression and phosphorylation of ABP may be contributing to the decrease in cell migration and septal formation in immature lungs injured by hyperoxia exposure. The differences between the findings in humans and mice are likely to be due to the early age of the mice, prior to onset of severe symptoms. Further investigations are needed to define the specific cell types affected and the role of actin binding proteins in lung development. Support or Funding Information This work was supported by the National Institutes of Health, NCCIH/ODS (LKR R01AT006880).