Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model

Nicole C Steiger-Luther1, Houda Darwiche1, Seh-Hoon Oh1, Jennifer M Williams1, Bryon E Petersen1,21Department of Pathology, Immunology and Laboratory Medicine, 2Program in Stem Cell Biology and Regenerative Medicine, College of Medicine, University of Florida, Gainesville, FL, USAAbstract: Oval cell...

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Autores principales:	Nicole C Steiger-Luther, Houda Darwiche, Seh-Hoon Oh, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/2d0ca67e71544636ba2a8be6aae6832e
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spelling	oai:doaj.org-article:2d0ca67e71544636ba2a8be6aae6832e2021-12-02T02:15:51ZInsulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model1179-1535https://doaj.org/article/2d0ca67e71544636ba2a8be6aae6832e2010-02-01T00:00:00Zhttp://www.dovepress.com/insulin-like-growth-factor-binding-protein-3-is-required-for-the-regul-a3940https://doaj.org/toc/1179-1535Nicole C Steiger-Luther1, Houda Darwiche1, Seh-Hoon Oh1, Jennifer M Williams1, Bryon E Petersen1,21Department of Pathology, Immunology and Laboratory Medicine, 2Program in Stem Cell Biology and Regenerative Medicine, College of Medicine, University of Florida, Gainesville, FL, USAAbstract: Oval cell-mediated liver regeneration is a highly complex process that involves the coordination of several signaling factors, chemokines and cytokines to allow for proper maintenance of the liver architecture. When hepatocyte proliferation is inhibited, an hepatic stem cell population, often referred to as &ldquo;oval cells&rdquo;, is activated to aid in liver regeneration. The function of insulin-like growth factor binding protein-3 (IGFBP-3) during this process of oval cell activation is of particular interest because it is produced in liver and has been shown to induce migration and differentiation of other stem cell populations both in vitro and in vivo. Additionally, IGFBP-3 production has been linked to the transforming growth factor-&beta; (TGF-&beta;) superfamily, a pathway known to be induced during oval cell proliferation. In this study, we set out to determine whether IGFBP-3 plays a role in oval cell proliferation, migration and differentiation during this specific type of regeneration. Through activation of the oval cell-mediated liver regeneration in a rat model, we found that IGFBP-3 is elevated in the liver and serum of animals during peak days of oval cell activation and proliferation. Furthermore, in vitro assays found that WB-344 cells, a liver stem cell line similar to oval cells, were induced to migrate in the presence of IGFBP-3. When expression of IGFBP-3 was knocked down during oval cell activation in vivo, we found that oval cell proliferation was increased and observed the appearance of numerous atypical ductular structures, which were OV-6 and Ki67-positive. Finally, quantitative realtime PCR analysis of liver tissue from IGFBP-3 small interfering RNA (siRNA) treated animals determined that expression of TGF&beta; family members, including TGF-&beta;RII and Smads 2&ndash;4, were significantly downregulated compared to animals at day 9 post-PHx alone or animals that received negative control siRNA. In conclusion, IGFBP-3 may function as a potent chemoattractant of oval cells during specific types of liver regeneration and may be involved in regulating oval cell proliferation and differentiation in vivo via the TGF-&beta; pathway.Keywords: hepatic stem cells, transforming growth factor-beta, N-2-acetylaminofluorene (2AAF), partial hepatectomy (PHx) Nicole C Steiger-LutherHouda DarwicheSeh-Hoon Ohet alDove Medical PressarticleDiseases of the digestive system. GastroenterologyRC799-869ENHepatic Medicine: Evidence and Research, Vol 2010, Iss default, Pp 13-32 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 Nicole C Steiger-Luther Houda Darwiche Seh-Hoon Oh et al Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model
description	Nicole C Steiger-Luther1, Houda Darwiche1, Seh-Hoon Oh1, Jennifer M Williams1, Bryon E Petersen1,21Department of Pathology, Immunology and Laboratory Medicine, 2Program in Stem Cell Biology and Regenerative Medicine, College of Medicine, University of Florida, Gainesville, FL, USAAbstract: Oval cell-mediated liver regeneration is a highly complex process that involves the coordination of several signaling factors, chemokines and cytokines to allow for proper maintenance of the liver architecture. When hepatocyte proliferation is inhibited, an hepatic stem cell population, often referred to as &ldquo;oval cells&rdquo;, is activated to aid in liver regeneration. The function of insulin-like growth factor binding protein-3 (IGFBP-3) during this process of oval cell activation is of particular interest because it is produced in liver and has been shown to induce migration and differentiation of other stem cell populations both in vitro and in vivo. Additionally, IGFBP-3 production has been linked to the transforming growth factor-&beta; (TGF-&beta;) superfamily, a pathway known to be induced during oval cell proliferation. In this study, we set out to determine whether IGFBP-3 plays a role in oval cell proliferation, migration and differentiation during this specific type of regeneration. Through activation of the oval cell-mediated liver regeneration in a rat model, we found that IGFBP-3 is elevated in the liver and serum of animals during peak days of oval cell activation and proliferation. Furthermore, in vitro assays found that WB-344 cells, a liver stem cell line similar to oval cells, were induced to migrate in the presence of IGFBP-3. When expression of IGFBP-3 was knocked down during oval cell activation in vivo, we found that oval cell proliferation was increased and observed the appearance of numerous atypical ductular structures, which were OV-6 and Ki67-positive. Finally, quantitative realtime PCR analysis of liver tissue from IGFBP-3 small interfering RNA (siRNA) treated animals determined that expression of TGF&beta; family members, including TGF-&beta;RII and Smads 2&ndash;4, were significantly downregulated compared to animals at day 9 post-PHx alone or animals that received negative control siRNA. In conclusion, IGFBP-3 may function as a potent chemoattractant of oval cells during specific types of liver regeneration and may be involved in regulating oval cell proliferation and differentiation in vivo via the TGF-&beta; pathway.Keywords: hepatic stem cells, transforming growth factor-beta, N-2-acetylaminofluorene (2AAF), partial hepatectomy (PHx)
format	article
author	Nicole C Steiger-Luther Houda Darwiche Seh-Hoon Oh et al
author_facet	Nicole C Steiger-Luther Houda Darwiche Seh-Hoon Oh et al
author_sort	Nicole C Steiger-Luther
title	Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model
title_short	Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model
title_full	Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model
title_fullStr	Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model
title_full_unstemmed	Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model
title_sort	insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2aaf/phx model
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/2d0ca67e71544636ba2a8be6aae6832e
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Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model

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