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Angiogenic Growth Factors secreted By Liver Epithelial Cells Modulate Arterial Vasculogenesis during Human Liver Development

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Abstract:

Intrahepatic bile ducts have close anatomical relationship with hepatic arteries. In liver disease, the arterial bed is extensively modulated following the expansion of “ductular reactive” cells. Recent experimental data (from ANIT fed rat, Hnf6 and Hnf1β KO mice) suggested that the development of the hepatic artery may be driven by unidentified signals originating from the bile duct.
We have thus investigated the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 and -2 (Ang-1, Ang-2) and their cognate receptors (VEGFR-1, VEGFR-2, Tie-2) by immunohistochemistry in 16 foetal liver specimens obtained from autopsy of spontaneous or medical abortion. Gestational age ranged from 10 to 36 weeks; 320 portal spaces were analyzed and stratified according to the biliary maturation stage in: ductal plate, migratory and incorporated bile duct stage. Double immunostainings for angiogenic factors and cell lineage phenotypic markers were performed using cytokeratin-7 (CK7) as biliary marker, CD34 as endothelial marker, smooth muscle actin (SMA) for mural cells.
Throughout the different developmental stages, Ang-1 was expressed by hepatoblasts and VEGF by developing bile ducts, but not by vascular cells. During the ductal plate stage, VEGFR-1 became positive in CD34+ cells arranged in discrete small cell clumps, VEGFR-2 was expressed by a different subset of CD34+ cells and Tie-2 by scattered spindle-shaped, ASMA+ cells. With the progressive bile duct incorporation into the portal space, CD34+ and SMA+ cells formed circular structures without lumen in proximity to the incorporating bile ducts. CD34+ cells expressed VEGFR-1, and SMA+ cells expressed both Tie-2 and Ang-2. In the incorporated bile duct stage this angiogenic profile was maintained, but SMA+ cells formed a thicker wall around CD34+ cells lining a well recognizable open lumen.
In conclusion, the presence of VEGF and Ang-1 in developing cholangiocytes and in hepatoblasts, respectively, and of their cognate receptors in endothelial and mural cells is consistent with a major role for angiogenic growth factors as mediators of the cross-talk between biliary epithelium and portal vasculature during human liver development. Cholangiocytes likely generate a VEGF gradient that determines arterial vasculogenesis in their vicinity while Ang-1 signaling from hepatoblasts contributes to the remodeling of hepatic arteries.
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Name: Connecticut's Stem Cell Research International Symposium
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URL: http://citation.allacademic.com/meta/p183090_index.html
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MLA Citation:

Cadamuro, Massimiliano., Fabris, Luca., Libbrecht, Louis., Spirli, Carlo., Fiorotto, Romina., Roskams, Tania. and Strazzabosco, Mario. "Angiogenic Growth Factors secreted By Liver Epithelial Cells Modulate Arterial Vasculogenesis during Human Liver Development" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, TBA, Hartford Connecticut, Mar 27, 2007 <Not Available>. 2013-12-16 <http://citation.allacademic.com/meta/p183090_index.html>

APA Citation:

Cadamuro, M. , Fabris, L. , Libbrecht, L. , Spirli, C. , Fiorotto, R. , Roskams, T. and Strazzabosco, M. , 2007-03-27 "Angiogenic Growth Factors secreted By Liver Epithelial Cells Modulate Arterial Vasculogenesis during Human Liver Development" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, TBA, Hartford Connecticut <Not Available>. 2013-12-16 from http://citation.allacademic.com/meta/p183090_index.html

Publication Type: Poster
Abstract: Intrahepatic bile ducts have close anatomical relationship with hepatic arteries. In liver disease, the arterial bed is extensively modulated following the expansion of “ductular reactive” cells. Recent experimental data (from ANIT fed rat, Hnf6 and Hnf1β KO mice) suggested that the development of the hepatic artery may be driven by unidentified signals originating from the bile duct.
We have thus investigated the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 and -2 (Ang-1, Ang-2) and their cognate receptors (VEGFR-1, VEGFR-2, Tie-2) by immunohistochemistry in 16 foetal liver specimens obtained from autopsy of spontaneous or medical abortion. Gestational age ranged from 10 to 36 weeks; 320 portal spaces were analyzed and stratified according to the biliary maturation stage in: ductal plate, migratory and incorporated bile duct stage. Double immunostainings for angiogenic factors and cell lineage phenotypic markers were performed using cytokeratin-7 (CK7) as biliary marker, CD34 as endothelial marker, smooth muscle actin (SMA) for mural cells.
Throughout the different developmental stages, Ang-1 was expressed by hepatoblasts and VEGF by developing bile ducts, but not by vascular cells. During the ductal plate stage, VEGFR-1 became positive in CD34+ cells arranged in discrete small cell clumps, VEGFR-2 was expressed by a different subset of CD34+ cells and Tie-2 by scattered spindle-shaped, ASMA+ cells. With the progressive bile duct incorporation into the portal space, CD34+ and SMA+ cells formed circular structures without lumen in proximity to the incorporating bile ducts. CD34+ cells expressed VEGFR-1, and SMA+ cells expressed both Tie-2 and Ang-2. In the incorporated bile duct stage this angiogenic profile was maintained, but SMA+ cells formed a thicker wall around CD34+ cells lining a well recognizable open lumen.
In conclusion, the presence of VEGF and Ang-1 in developing cholangiocytes and in hepatoblasts, respectively, and of their cognate receptors in endothelial and mural cells is consistent with a major role for angiogenic growth factors as mediators of the cross-talk between biliary epithelium and portal vasculature during human liver development. Cholangiocytes likely generate a VEGF gradient that determines arterial vasculogenesis in their vicinity while Ang-1 signaling from hepatoblasts contributes to the remodeling of hepatic arteries.

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