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Modulation of hepatocyte and sinusoidal endothelial cell responses by ectonucleotidase during liver regeneration

English title Modulation of hepatocyte and sinusoidal endothelial cell responses by ectonucleotidase during liver regeneration
Applicant Beldi Guido
Number 112764
Funding scheme Fellowships for prospective researchers
Research institution Research North Beth Israel Deaconess Medical Center Harvard University
Institution of higher education Institution abroad - IACH
Main discipline Surgery
Start/End 01.01.2006 - 31.12.2006
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All Disciplines (2)

Discipline
Surgery
Pathophysiology

Keywords (6)

liver regeneration; hepatocyte; purinergic signaling; CN39; hepatic sinusoidal endothelia cell; ectonucleotidases

Lay Summary (English)

Lead
Lay summary
Liver failure after sub-total hepatectomy and primary graft failure following liver transplantation are both clinical conditions associated with impaired liver regeneration. In this context, liver failure is thought to develop as a consequence of insufficient hepatic mass.Therapies directed at augmenting hepatocyte and sinusoidal cell proliferation in an orchestrated manner could be of benefit in these clinical scenarios.
Ectonucleotidases (e.g. NTPDase1 known as CD39) are expressed by hepatic sinusoidal endothelial cells and appear to play a critical role in mediating vascular inflammation and angiogenesis. In vascular endothelial cell signaling ectonucleotidases interact with adenosine and vascular endothelial growth factor (VEGF). In hepatocyte cell signaling ectonucleotidases are potentially involved by modifying RanBPM and the MET receptor. In this proposal, we will investigate the signaling of sinusoidal endothelial cells and hepatocytes during liver regeneration in an animal model, studying mice null for cd39, the dominant vascular ectonucleotidase.
Specific aim 1: To analyze outcomes and kinetics of hepatocyte and sinusoidal endothelial cell proliferation in mice null for cd39 in liver regeneration.
Specific aim 2: To analyze the interrelationship of NTPDase1, RanBPM on MET receptor activation in hepatocytes.
Specific aim 3: To analyze the interrelationship of NTPDase1, VEGF and adenosine on sinusoidal endothelial cell proliferation.
These experiments will elucidate the potential role of ectonucleotidases upon purinergic signaling in both sinusoidal endothelial cells and hepatocytes during liver regeneration. The studies will provide a better understanding of both mechanism of liver regeneration and the interaction between sinusoidal endothelial cells and hepatocytes. This work may provide information for the development of novel therapeutic avenues for liver regeneration, as nucleotides are small compounds, and derivatives could be administered orally or parenterally.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Associated projects

Number Title Start Funding scheme
146986 NTPDase1/CD39 and innate lymphoid cells in liver injury and repair 01.04.2013 Project funding
130816 Natural killer cell function after liver resection: the role of extracellular ATP 01.04.2010 Project funding
166594 Purinergic control of innate lymphoid cells in liver injury and repair 01.04.2016 Project funding

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