Porcine insulin-like growth factor (IGF)-binding protein-3 elicits bi-phasic effects on IGF-I stimulated DNA synthesis in neonatal porcine skin fibroblasts |
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| Affiliation: | 1. Department of Cell Biology Baylor College of Medicine Houston, TX 77030 USA;7. Department of Dairy and Animal Science The Pennsylvania State University University Park, PA 16802 USA;1. Brighton and Sussex University Hospitals NHS Trust, Brighton, UK;2. Royal Devon and Exeter NHS Foundation Trust, Exeter, UK and University of Exeter Medical School, Exeter, UK;3. NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK;4. Royal Devon and Exeter NHS Foundation Trust and University of Exeter Medical School, Exeter, UK;5. University of Exeter Medical School and Royal Devon and Exeter NHS Foundation Trust, Exeter, UK;1. CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium;2. Clinique St Luc, Bouge, Belgium;3. CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium;4. Université de Paris, AP-HP, Hôpital Beaujon, Service d''Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, VALDIG Group, Centre de recherche sur l''inflammation, Inserm, UMR 1149, Paris, France;5. Hôpital Trousseau, CHU de Tours, FILFOIE, ERN RARE-LIVER, VALDIG Group, Tours, France;6. IRCCS Fondazione Ca'' Granda – Ospedale Maggiore Policlinico, ERN RARE-LIVER, VALDIG Group, Milan, Italy;7. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;8. Barcelona Hepatic Hemodynamic Lab, Clinic Barcelona Hospital, CIBEREHD, IDIBAPS, Universitat de Barcelona, ERN RARE-LIVER, VALDIG Group, Barcelona, Spain;9. CHU, Besançon, France;10. Royal Free Hospital, London, UK;11. Algemeen Stedelijk Ziekenhuis ASZ, Aalst, Belgium;12. CHU, Lille, France;13. Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania;14. Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria;15. Hôpital Universitaire Rangueil Toulouse, FILFOIE, ERN RARE-LIVER, VALDIG Group, Toulouse, France;16. Hôpital Universitaire Charles Nicolle de Rouen, Rouen, France;17. Hôpital Universitaire Côte de la Nacre, FILFOIE, ERN RARE-LIVER, VALDIG Group, Caen, France;18. Paris Cité University, AP-HP, Beaujon Hospital, Intestinal Stroke Center, Gastroenterology, IBD, Intestinal Failure Department, Inserm, UMR 1148, Paris, France;1. Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia;2. Centenary Institute and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia;3. Phage Consulting, Sydney, NSW, Australia;4. The Evergreen State College, Olympia, WA, USA;5. Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia |
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| Abstract: | The present study was undertaken to investigate the effects of porcine IGFBP-3 on IGF-I stimulated DNA synthesis in neonatal porcine skin fibroblasts. IGF-1 stimulated DNA synthesis in skin fibroblasts in a concentration dependent manner. DNA synthesis was maximally stimulated by 5 to 20 fold at 5 nM IGF-I; half-maximal stimulation was observed at approximately 1 nM IGF-I. Co-incubation of IGFBP-3 with a maximally effective dose of IGF-I (10 nM) did not inhibit the stimulatory effects of IGF-I on DNA synthesis. In contrast, when IGFBP-3 at concentrations of 0 to 20 nM was co-incubated with 1 nM IGF-I, a bi-phasic dose response was observed with IGFBP-3 being inhibitory only at a 10 to 20 fold molar excess to IGF-I. Based on the approximately equal molar ratio of IGFBP-3:IGF-I present in the circulation of control and pST-treated pigs our results suggest that IGFBP-3 does not inhibit the mitogenic effects of IGF-I. In summary, these results indicate that the combination of IGFBP-3 with IGF-I optimizes mitogenic signalling via the type I IGF receptor and suggest that IGFBP-3 does not inhibit the effects of ST that are mediated by IGF-I. |
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