Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development
- Author
- Luca Fabris, Massimiliano Cadamuro, Louis Libbrecht (UGent) , Peggy Raynaud, Carlo Spirli, Romina Fiorotto, Lajos Okolicsanyi, Frederic Lemaigre, Mario Strazzabosco and Tania Roskams
- Organization
- Abstract
- Intrahepatic bile ducts maintain a dose 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. 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.
- Keywords
- INTRAHEPATIC BILE-DUCTS, PERIBILIARY CAPILLARY PLEXUS, CELL-ADHESION MOLECULE, TIE2 RECEPTOR, CHOLANGIOCYTE PROLIFERATION, HEPATIC-ARTERY, PRIMARY DEFECT, BILIARY-TRACT, ANGIOPOIETIN-1, VASCULARIZATION
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-3183695
- MLA
- Fabris, Luca, et al. “Epithelial Expression of Angiogenic Growth Factors Modulate Arterial Vasculogenesis in Human Liver Development.” HEPATOLOGY, vol. 47, no. 2, 2008, pp. 719–28, doi:10.1002/hep.22015.
- APA
- Fabris, L., Cadamuro, M., Libbrecht, L., Raynaud, P., Spirli, C., Fiorotto, R., … Roskams, T. (2008). Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. HEPATOLOGY, 47(2), 719–728. https://doi.org/10.1002/hep.22015
- Chicago author-date
- Fabris, Luca, Massimiliano Cadamuro, Louis Libbrecht, Peggy Raynaud, Carlo Spirli, Romina Fiorotto, Lajos Okolicsanyi, Frederic Lemaigre, Mario Strazzabosco, and Tania Roskams. 2008. “Epithelial Expression of Angiogenic Growth Factors Modulate Arterial Vasculogenesis in Human Liver Development.” HEPATOLOGY 47 (2): 719–28. https://doi.org/10.1002/hep.22015.
- Chicago author-date (all authors)
- Fabris, Luca, Massimiliano Cadamuro, Louis Libbrecht, Peggy Raynaud, Carlo Spirli, Romina Fiorotto, Lajos Okolicsanyi, Frederic Lemaigre, Mario Strazzabosco, and Tania Roskams. 2008. “Epithelial Expression of Angiogenic Growth Factors Modulate Arterial Vasculogenesis in Human Liver Development.” HEPATOLOGY 47 (2): 719–728. doi:10.1002/hep.22015.
- Vancouver
- 1.Fabris L, Cadamuro M, Libbrecht L, Raynaud P, Spirli C, Fiorotto R, et al. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. HEPATOLOGY. 2008;47(2):719–28.
- IEEE
- [1]L. Fabris et al., “Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development,” HEPATOLOGY, vol. 47, no. 2, pp. 719–728, 2008.
@article{3183695, abstract = {{Intrahepatic bile ducts maintain a dose 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. 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.}}, author = {{Fabris, Luca and Cadamuro, Massimiliano and Libbrecht, Louis and Raynaud, Peggy and Spirli, Carlo and Fiorotto, Romina and Okolicsanyi, Lajos and Lemaigre, Frederic and Strazzabosco, Mario and Roskams, Tania}}, issn = {{0270-9139}}, journal = {{HEPATOLOGY}}, keywords = {{INTRAHEPATIC BILE-DUCTS,PERIBILIARY CAPILLARY PLEXUS,CELL-ADHESION MOLECULE,TIE2 RECEPTOR,CHOLANGIOCYTE PROLIFERATION,HEPATIC-ARTERY,PRIMARY DEFECT,BILIARY-TRACT,ANGIOPOIETIN-1,VASCULARIZATION}}, language = {{eng}}, number = {{2}}, pages = {{719--728}}, title = {{Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development}}, url = {{http://doi.org/10.1002/hep.22015}}, volume = {{47}}, year = {{2008}}, }
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