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Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2008 Feb; Vol. 47 (2), pp. 719-28. - Publication Year :
- 2008
-
Abstract
- Unlabelled: Intrahepatic bile ducts maintain a close anatomical relationship with hepatic arteries. During liver ontogenesis, the development of the hepatic artery appears to be modulated by unknown signals originating from the bile duct. Given the capability of cholangiocytes to produce angiogenic growth factors and influence peribiliary vascularization, we studied the immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietin-1, angiopoietin-2, and their cognate receptors (VEGFR-1, VEGFR-2, Tie-2) in fetal human livers at different gestational ages and in mice characterized by defective biliary morphogenesis (Hnf6(-/-)). The results showed that throughout the different developmental stages, VEGF was expressed by developing bile ducts and angiopoietin-1 by hepatoblasts, whereas their cognate receptors were variably expressed by vascular cells according to the different maturational stages. Precursors of endothelial and mural cells expressed VEGFR-2 and Tie-2, respectively. In immature hepatic arteries, endothelial cells expressed VEGFR-1, whereas mural cells expressed both Tie-2 and Angiopoietin-2. In mature hepatic arteries, endothelial cells expressed Tie-2 along with VEGFR-1. In early postnatal Hnf6(-/-) mice, VEGF-expressing ductal plates failed to incorporate into the portal mesenchyma, resulting in severely altered arterial vasculogenesis.<br />Conclusion: The reciprocal expression of angiogenic growth factors and receptors during development supports their involvement in the cross talk between liver epithelial cells and the portal vasculature. Cholangiocytes generate a VEGF gradient that is crucial during the migratory stage, when it determines arterial vasculogenesis in their vicinity, whereas angiopoietin-1 signaling from hepatoblasts contributes to the remodeling of the hepatic artery necessary to meet the demands of the developing epithelium.
- Subjects :
- Animals
Bile Ducts embryology
Gestational Age
Hepatocyte Nuclear Factor 6 deficiency
Humans
Mice
Mice, Knockout
Portal System embryology
Portal System pathology
Portal System physiology
Epithelial Cells physiology
Growth Substances physiology
Hepatic Artery cytology
Hepatic Artery physiology
Liver cytology
Liver embryology
Neovascularization, Physiologic
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 47
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 18157837
- Full Text :
- https://doi.org/10.1002/hep.22015