Cholelithiasis-induced cholestasis is one of the most common causes of hospitalization due to gastrointestinal disease,yet considerable knowledge gaps exist in the pathogenesis of this disease.This can partially be ex...Cholelithiasis-induced cholestasis is one of the most common causes of hospitalization due to gastrointestinal disease,yet considerable knowledge gaps exist in the pathogenesis of this disease.This can partially be explained by inadequate characterization of experimental cholestasis models.Here,we compared the transcriptional profile of commonly used mouse models for obstructive cholestasis and benchmarked them to human disease to identify the model(s)best suited for cholelithiasis-induced cholestasis research and to uncover conserved mechanisms involved in human and murine cholestasis.展开更多
Direct intercellular communication mediated by gap junctions constitutes a major regulatory platform in the control of hepatic homeostasis.Hepatocellular gap junctions are composed of two hemichannels of adjacent cell...Direct intercellular communication mediated by gap junctions constitutes a major regulatory platform in the control of hepatic homeostasis.Hepatocellular gap junctions are composed of two hemichannels of adjacent cells which are built up by connexin proteins,in casu Cx32.Mathieu Vinken,Pofessor at the Department of Toxicology of the Free University BrusselsBelgium,was one of the first investigators to demonstrate that hepatic connexin expression is controlled by epigenetic mechanisms.In particular,he found that inhibitors of histone deacetylase enzymes enhance Cx32 production and gap junction activity in cultures of primary hepatocytes,a finding that is of importance for liver-based in vitro modelling.Professor Dr.Mathieu Vinken's recent work is focussed on the elucidation of the role of connexin proteins and their channels in the hepatocyte life cycle.Specific attention is paid to apoptosis in this context,whereby it has been found that Cx32 hemichannels control the termination of induced cell death in cultures of primary hepatocytes. Overall,Professor Dr.Mathieu Vinken's research can be considered as an important contribution to the field of hepatic connexin physiology.展开更多
Connexin hemichannels have long been considered asmere structural precursors for gap junctions.In the last decade,it has become clear that they also act as individual channels,connecting the intracellular compartment ...Connexin hemichannels have long been considered asmere structural precursors for gap junctions.In the last decade,it has become clear that they also act as individual channels,connecting the intracellular compartment and the extracellular environment.Impairement of connexin hemichannel functionality may result in disturbance of homeostasis,as exemplified in the current paper for the intestine and the liver.Research in this field still has a number of shortcomings,of which some are also discussed here.展开更多
基金This work was supported by a doctoral grant strategic basic research with application number 1S47219N from Research Foundation-Flanders,Belgium and the Special Research Fund-UGent.
文摘Cholelithiasis-induced cholestasis is one of the most common causes of hospitalization due to gastrointestinal disease,yet considerable knowledge gaps exist in the pathogenesis of this disease.This can partially be explained by inadequate characterization of experimental cholestasis models.Here,we compared the transcriptional profile of commonly used mouse models for obstructive cholestasis and benchmarked them to human disease to identify the model(s)best suited for cholelithiasis-induced cholestasis research and to uncover conserved mechanisms involved in human and murine cholestasis.
基金supported by grants of the FWO,the research council of the VUB and the European Union
文摘Direct intercellular communication mediated by gap junctions constitutes a major regulatory platform in the control of hepatic homeostasis.Hepatocellular gap junctions are composed of two hemichannels of adjacent cells which are built up by connexin proteins,in casu Cx32.Mathieu Vinken,Pofessor at the Department of Toxicology of the Free University BrusselsBelgium,was one of the first investigators to demonstrate that hepatic connexin expression is controlled by epigenetic mechanisms.In particular,he found that inhibitors of histone deacetylase enzymes enhance Cx32 production and gap junction activity in cultures of primary hepatocytes,a finding that is of importance for liver-based in vitro modelling.Professor Dr.Mathieu Vinken's recent work is focussed on the elucidation of the role of connexin proteins and their channels in the hepatocyte life cycle.Specific attention is paid to apoptosis in this context,whereby it has been found that Cx32 hemichannels control the termination of induced cell death in cultures of primary hepatocytes. Overall,Professor Dr.Mathieu Vinken's research can be considered as an important contribution to the field of hepatic connexin physiology.
基金Supported partially by the Fund for Scientific Research Flanders(FWO-Vlaanderen),Belgium
文摘Connexin hemichannels have long been considered asmere structural precursors for gap junctions.In the last decade,it has become clear that they also act as individual channels,connecting the intracellular compartment and the extracellular environment.Impairement of connexin hemichannel functionality may result in disturbance of homeostasis,as exemplified in the current paper for the intestine and the liver.Research in this field still has a number of shortcomings,of which some are also discussed here.
