Mechanisms of therapeutic action of IGF-I in cirrhosis and hepatocarcinoma: studies in experimental cirrhosis, cell lines and human liver (Q3191280): Difference between revisions
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(Created claim: summary (P836): IGF-I is very deficient in cirrhosis due to decreased liver synthesis. Exogenous IGF-I or the restoration of liver synthesis by gene therapy completely or partially reverses cirrhosis and appears to decrease the risk of hepatocarcinoma. The aim is to identify the underlying mechanisms. 1. Analysis of novel molecular mechanisms induced by IGF-I (evaluation in cirrhotic, cirrhotic rats transduced to produce IGF-I via VPA vector and controls): 1.1....) |
(Changed label, description and/or aliases in en: translated_label) |
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Mechanisms of therapeutic action of IGF-I in cirrhosis and hepatocarcinoma: studies in experimental cirrhosis, cell lines and human liver | |||
Revision as of 21:45, 12 October 2021
Project Q3191280 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Mechanisms of therapeutic action of IGF-I in cirrhosis and hepatocarcinoma: studies in experimental cirrhosis, cell lines and human liver |
Project Q3191280 in Spain |
Statements
39,250.0 Euro
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78,500.0 Euro
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50.0 percent
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1 January 2014
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31 March 2017
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UNIVERSIDAD DE NAVARRA
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42°49'6.42"N, 1°38'39.34"W
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31201
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IGF-I es muy deficiente en la cirrosis por disminución de síntesis hepática. IGF-I exógeno o la restauración de su síntesis hepática mediante terapia génica revierten total o parcialmente la cirrosis y parecen disminuir el riesgo de hepatocarcinoma. El objetivo es identificar los mecanismos subyacentes. 1. Análisis de mecanismos moleculares novedosos inducidos por IGF-I (evaluación en ratas cirróticas, cirróticas transducidas para producir IGF-I mediante vector AAV y controles): 1.1.Evaluación de la función mitocondrial y metabolismo energético: consumo de oxígeno, potencial de membrana, cuantificación de especies reactivas de oxígeno, ATP, AMP, NAD, NADH, fosforilación de AMPc y acetilación inducida por SIRT1. 1.2. Estudio del estado del ritmo circadiano: melatonina sérica y expresión de mRNAs y proteínas clave del ritmo circadiano durante las 24 horas. 1.3.Análisis de factores femeninos en el hígado masculino que expresa IGF-I: receptores de estrógenos y andrógenos e identificación del tipo celular en que se expresan. 2. Análisis de mecanismos moleculares novedosos inducidos por IGF-I en células en cultivo (hepatocitos y células estelares aisladas y en cocultivo) : valoración del efecto de IGF-I y HGF sobre función mitocondrial, expresión de receptores estrogénicos y ciclo circadiano. 3. Análisis del hígado de pacientes cirróticos y controles sanos: función mitocondrial, receptores estrogénicos y ritmo circadiano. 4. Evaluación del papel del IGF-I en el desarrollo y progresión del hepatocarcinoma: animales con hepatocarcinoma inducido por DEN en ratones KO para IGF-I y valoración del efecto de líneas celulares introducidas en estos hígados y transducidas para producir IGF-I, IGF-II o control inactivo (Spanish)
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IGF-I is very deficient in cirrhosis due to decreased liver synthesis. Exogenous IGF-I or the restoration of liver synthesis by gene therapy completely or partially reverses cirrhosis and appears to decrease the risk of hepatocarcinoma. The aim is to identify the underlying mechanisms. 1. Analysis of novel molecular mechanisms induced by IGF-I (evaluation in cirrhotic, cirrhotic rats transduced to produce IGF-I via VPA vector and controls): 1.1.Evaluation of mitochondrial function and energy metabolism: oxygen consumption, membrane potential, quantification of reactive oxygen species, ATP, AMP, NAD, NADH, AMPc phosphorylation and SIRT-induced acetylation1. 1.2. Study of the state of circadian rhythm: serum melatonin and expression of mRNAs and key proteins of circadian rhythm during 24 hours. 1.3.Analysis of female factors in the male liver expressing IGF-I: estrogen and androgen receptors and identification of the cell type in which they are expressed. 2. Analysis of novel molecular mechanisms induced by IGF-I in cultured cells (hepatocytes and isolated and cocultivated stellar cells): assessment of the effect of IGF-I and HGF on mitochondrial function, expression of estrogenic receptors and circadian cycle. 3. Liver analysis of cirrhotic patients and healthy controls: mitochondrial function, estrogenic receptors and circadian rhythm. 4. Evaluation of the role of IGF-I in the development and progression of hepatocarcinoma: animals with DEN-induced hepatocarcinoma in KO mice for IGF-I and assessment of the effect of cell lines introduced into these livers and transduced to produce IGF-I, IGF-II or inactive control (English)
12 October 2021
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Pamplona/Iruña
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Identifiers
PI13_01989
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