title: Postnatal hyperoxia exposure differentially affects hepatocytes and liver haemopoietic cells in newborn rats.
abstract: Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized.
authors.affiliation: Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Guya Diletta
authors.initials: GD
authors.lastname: Marconi
authors.affiliation: Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Susi
authors.initials: S
authors.lastname: Zara
authors.affiliation: Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: De Colli
authors.affiliation: Department of Medicine and Ageing Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Valerio
authors.affiliation: Institute of Molecular Genetics CNR, Unit of Chieti, Chieti, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Rapino
authors.affiliation: Neonatal Intensive Care Unit, Women's and Children's Health Department, University of Padova, Padova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zaramella
authors.affiliation: Neonatal Intensive Care Unit, Women's and Children's Health Department, University of Padova, Padova, Italy.
authors.forename: Arben
authors.initials: A
authors.lastname: Dedja
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Macchi
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caro
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Porzionato
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat