The Interaction Of Hepatic Stellate Cells And Liver Stem Cells In The Senescent Liver

Senescence is a basic biological phenomenon,usually develops in elderly individuals.Studies have shown that,senescence is closely related with tissue stem cell functions.In our study,it is found that the murine liver senesces with age,and in the senescent liver,the mobilization capability of liver stem cells is decreased.It is generally believed that liver stem cells originate in the terminal structure of intrahepatic bile duct,namely the Canals of Hering.In mice,due to its oval shape and high nucleocytoplasmic ratio,liver stem cells are also known as oval cells,rare and generally in the resting state.In this study,animal models were used to induce the activation and proliferation of oval cells.In senescent liver,these cells were hardly mobilized.After total liver tissue microarry screening,it was found that certain extracellular matrix proteins decreased significantly in aging mice liver.As is known,extracellular matrix proteins are mainly produced by hepatic stellate cells(HSC).They exist in Disse's space and are quiescent under physiological status,upon liver injury,they transdifferentiate into myofibroblasts and produce lots of extracellular matrix components to participate in the liver repair.In aging liver,the HSCs are less activated,the reduced extracellular matrix proteins production is a key factor leading to decreased mobilization of oval cells,among these extracellular matrix proteins,laminin plays the most important role.Laminin constitutes the microenvironment of oval cells(niche),it can also promotes the biological function such as proliferation of oval cells,and then provide effective support for oval cell mobilization.In the other hand,activated oval cells can promote the activation of HSCs as well,this intercellular interaction regulates liver injury repair.To sum up,in our study,we found that the murine liver senesces with age,senescence-associated proteins upregulated,liver structure was destroyed,hepatocytes degeneration,inflammatory cells infiltration and so on.On the other hand,the activation ability of HSCs was reduced in aging mice liver with injury,they produced less extracellular matrix proteins,leading to declined mobilization of oval cells,and liver repair dysfunction.Meanwhile,oval cells could support the activation of HSCs and the production of extracellular matrix proteins,the cross talk between these two types of cells may regulate the liver repair together.The regulation of key factors and signal pathways involved in oval cells and HSCs interaction may provide a new strategy for clinical treatment of liver injury related diseases.