title: Transient GFER knockdown in vivo impairs liver regeneration after partial hepatectomy.
abstract: OBJECTIVE
  Augmenter of Liver Regeneration is a protein encoded by the Growth Factor Erv1-Like gene. Its biological properties are crucial for cell survival since knock-out mice for Growth Factor Erv1-Like gene do not survive. In this study, we injected hepatotropic adenoviral particles harboring oligonucleotide sequences against Growth Factor Erv1-Like gene into 70% partially hepatectomized rats and studied the effect of gene silencing on the progression liver regeneration.
  
  
  METHODS
  Partially hepatectomized rats were divided into three groups of animals and, before surgery, received either phosphate buffer saline, or adenoviral particles alone or adenoviral particles harboring the oligonucleotide silencing sequence. In each group, rats were sacrificed at 12, 24 and 48 h after surgery. Liver tissues were collected to analyze the expression of Augmenter of Liver Regeneration, Bax, Bcl-2 and activated Caspase-9 and -3, as well as hepatocyte proliferation and apoptosis, polyamines levels and histological and ultrastructural features.
  
  
  RESULTS
  Growth Factor Erv1-Like gene silencing reduced the compensatory hepatocellular proliferation triggered by surgery through (i) the reduction of polyamines synthesis, hepatocyte proliferation and anti-apoptotic gene expression and (ii) the increase of pro-apoptotic gene expression and caspase activation.
  
  
  CONCLUSIONS
  For the first time, using a technique of gene silencing in vivo, our results demonstrate that Growth Factor Erv1-Like gene knock-down, i.e., the lack of Augmenter of Liver Regeneration, modifies the expression of genes involved in cell apoptosis and inhibits early phase of DNA synthesis. As a consequence, a promotion of cell death and a reduction of cell proliferation occurs.
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy. Electronic address: direzionescientifica@irccsdebellis.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Francavilla
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pesetti
authors.affiliation: Section of Gastroenterology, DMSS, University of Foggia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.affiliation: Consorzio M. Negri Sud, Santa Maria Imbaro (CH), Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Morgano
authors.affiliation: IRCCS Oncologico Giovanni Paolo II, Bari, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Bovenga
authors.affiliation: Section of Anatomy Pathology, DETO, University of Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Napoli
authors.affiliation: Section of Anatomy Pathology, DETO, University of Bari, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Resta
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Russo
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Linsalata
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Minoia
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy.
authors.forename: Giusy
authors.initials: G
authors.lastname: Bianco
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Tafaro
authors.affiliation: IRCCS "S. de Bellis", Castellana Grotte, Bari, Italy; Section of Gastroenterology, DETO, University of Bari, Italy; Center Interdept. of Res. on Gastroent. and Hepat. of Age of Development (CIRGEEE), University of Bari, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Polimeno
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006498:Hepatectomy; D006801:Humans; D008107:Liver Diseases / Q000235:genetics* / Q000628:therapy; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D051381:Rats
chemical_list: D011506:Proteins; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors; C551231:GFER protein, mouse
keywords: Adenovirus; Apoptosis; Gene silencing; Growth Factor Erv1-Like gene (GFER); Mitochondria