Expression Patterns And Action Analysis Of Rat Liver Regeneration Associated Genes

It has been well characterized that the liver has very strong capability to regenerate and restore its normal mass and function by rapid liver cells proliferation after partial hepatectomy(PH),or injury caused by chemicals or biological stimuli,which is so-called liver regeneration.The liver regeneration progress involves a series of biological process including cell activation, dedifferentiation,proliferation and its regulation,redifferentiation,structure-functional reorganization,and during which the reconstruction of following activities,such as extracelhlar matrix,cell junction,cytoskeleton,cell migration and membrane protein,very necessarily take place. And a large number of data shows that above activities involve mutiple genes.The previous studies mainly focused on the function of the separate gene associated with extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein during liver regeneration,but the combined effect of these genes by far is rarely mentioned.This time,automatically high-throughput technique and system biological method come into play and become the potent tools for studying the global expression and the integrated function of genes involved in extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein during liver regeneration.In this study,the genes participating in the mentioned-above biological activities were obtained through retrieving the data from professional websites and searching for scientific documents,Rat Genome 230 2.0 chip was applied to detected their expression changes during rat liver regeneration and screened out the liver regeneration-associated genes utilizing liver tissues at different time points after PH as experimental materials;and the expression alterations,expression patterns and action duration,and interaction among liver regeneration-associated genes involved in extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein were investigated through system biological method for exploring the function of extracellular matrix,cell junction, cytoskeleton,cell migration,membrane protein during liver regeneration.To verify validity of chip results,this study detected the mRNA abundance of four randomly chosen genes including alb,pklr,prkaa1,trim24 by using fluorescence quantitative PCR,and then compared results of quantitative RT-PCR with that of oligonucleotide chips.The cluster analysis and expression patterns analysis demonstrate that genes participating in extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein arc quite different,and their expression patterns and time relevance are also distinct.The dynamic analysis of gene expressions demonstrates that these genes start expressing largely at initiation phase of liver regeneration and work at different phases.36%genes are elevated in expression,level while 30% attenuated.Time relevance analysis of gene expression suggests that genes participating in extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein operate at different phases.The analysis results are showed as follows:(1) Among 196 genes participating in extracellular matrix,97 genes are associated with liver regeneration,having five expression trends, six time-relevant groups,six expression patterns and 1916 relations.(2) Among 558 genes participating in cell junction,256 genes are associated with liver regeneration,exhibiting five expression trends,four time-relevant groups,twenty-three expression patterns and 1916 relations.(3) Among 840 cytoskeleton-participating genes,249 genes are associated with liver regeneration, exhibiting five expression trends,four time-relevant groups,twenty-one expression patterns and 1316 relations.(4) Among 326 cell migration-participating genes,176 genes are associated with liver regeneration,exhibiting five expression trends,six time-relevant groups,four expression patterns and 1749 relations.(5) Among 1898 membrane protein-participating genes,788 genes are associated with liver regeneration,exhibiting five expression trends,five time-relevant groups, twenty-three expression patterns and 3921 relations.The analysis on comparison of oligonucleotide chip results and quantitative RT-PCR results demonstrates that chip results of this experiment have comparatively high reliability.The genes associated with extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein are all promoted in expression,and they play important roles in structural-function reconstitution of regenerating liver.However,the process(genes→mRNA→protein) was infulenced by multiple factors including protein interaction.It strongly needs to further investigate proteomically on the expression changes,interactions and action mechanism of the corresponding proteins in extracellular matrix,cell junction,cytoskeleton,cell migration and membrane protein. With the research increasingly deepening,the new problems emerge one by one.For example,the study on liver regeneration regulators currently primarily concentrates on the promoting factors,but very little on the inhibitor factor.Also,it is unclear how the non-specific promoting factors control regeneration progress,now these questions need to be further researched.