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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Anticuerpos monoclonales > DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista >

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration
Authors: Beraza, N. (Naiara)
Marques, J.M. (Juan Martín)
Martinez-Anso, E. (Eduardo)
Iñiguez, M. (María)
Prieto, J. (Jesús)
Bustos, M. (Matilde)
Keywords: Cytokines/physiology
Liver Regeneration
Prostaglandins/physiology
Vascular Endothelial Growth Factor A/physiology
Issue Date: 2005
Publisher: Wiley Blackwell
Publisher version: http://dx.doi.org/10.1002/hep.20590
ISSN: 0270-9139
Citation: Beraza N, Marques JM, Martinez-Anso E, Iñiguez M, Prieto J, Bustos M. Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration. Hepatology 2005 Mar;41(3):460-469.
Abstract
Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis.
Permanent link: http://hdl.handle.net/10171/20333
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista

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