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Surfactant metabolism and anti-oxidative capacity in hyperoxic neonatal rat lungs: effects of keratinocyte growth factor on gene expression in vivo

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Abstract

Development of preterm infant lungs is frequently impaired resulting in bronchopulmoary dysplasia (BPD). BPD results from interruption of physiologic anabolic intrauterine conditions, the inflammatory basis and therapeutic consequences of premature delivery, including increased oxygen supply for air breathing. The latter requires surfactant, produced by alveolar type II (AT II) cells to lower surface tension at the pulmonary air:liquid interface. Its main components are specific phosphatidylcholine (PC) species including dipalmitoyl-PC, anionic phospholipids and surfactant proteins. Local antioxidative enzymes are essential to cope with the pro-inflammatory side effects of normal alveolar oxygen pressures. However, respiratory insufficiency frequently requires increased oxygen supply. To cope with the injurious effects of hyperoxia to epithelia, recombinant human keratinocyte growth factor (rhKGF) was proposed as a surfactant stimulating, non-catabolic and epithelial-protective therapeutic. The aim of the present study was to examine the qualification of rhKGF to improve expression parameters of lung maturity in newborn rats under hyperoxic conditions (85 % O2 for 7 days). In response to rhKGF proliferating cell nuclear antigen mRNA, as a feature of stimulated proliferation, was elevated. Similarly, the expressions of ATP-binding cassette protein A3 gene, a differentiation marker of AT II cells and of peroxiredoxin 6, thioredoxin and thioredoxin reductase, three genes involved in oxygen radical protection were increased. Furthermore, mRNA levels of acyl-coA:lysophosphatidylcholine acyltransferase 1, catalyzing dipalmitoyl-PC synthesis by acyl remodeling, and adipose triglyceride lipase, considered as responsible for fatty acid supply for surfactant PC synthesis, were elevated. These results, together with a considerable body of other confirmative evidence, suggest that rhKGF should be developed into a therapeutic option to treat preterm infants at risk for impaired lung development.

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Acknowledgments

The authors thank Petra Peche, Verena Müller and Silvia Bramke for excellent technical assistance. R. Koslowski was supported by German Research Council Projects (KO 2219/4-1 and KO 2219/4-2), R. Koslowski and M. Lange were supported by “Roland Ernst Stiftung für Gesundheitswesen”. W. Bernhard was supported by an institutional grant of the medical faculty of the University of Tübingen (F.1275089) and by German Research Council Project BE2223/2.

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  1. Institute of Physiological Chemistry, Medical Faculty “Carl Gustav Carus”, University of Technology Dresden, Fiedlerstr 42, 01307, Dresden, Germany

    Roland Koslowski & Marco Lange

  2. Institute of Anatomy, Faculty of Medicine, University of Technology, Dresden, Germany

    Michael Kasper & Lilla Knels

  3. Department of Neonatology, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany

    Katharina Schaal & Wolfgang Bernhard

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  1. Roland Koslowski
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Correspondence to Roland Koslowski.

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Koslowski, R., Kasper, M., Schaal, K. et al. Surfactant metabolism and anti-oxidative capacity in hyperoxic neonatal rat lungs: effects of keratinocyte growth factor on gene expression in vivo. Histochem Cell Biol 139, 461–472 (2013). https://doi.org/10.1007/s00418-012-1038-9

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