Balance proliferación/muerte celular en la historia natural de la cirrosis hepática experimental

Chronic liver disease is defined as the progressive deterioration of liver function due to a continuous process of inflammation, destruction, and regeneration of liver parenchyma that leads to the development of fibrosis and cirrhosis. Despite being a well-studied disease, it is still the world's 11th most common cause of death and represents a global public health issue. Variations in liver size may help determine the stage of chronic liver disease. The relationship between changes in liver size and the expression levels of certain genes and proteins, as well as other pathophysiological factors associated with liver disease, have not been studied in depth, but it could reveal new approaches for diagnosis and treatment. The aim of this study was to determine the relationship between the disease stage (as determined by the liver weight-to-body weight ratio) and the changes in protein and gene expression associated with cell proliferation and cell death in liver tissue from rats with carbon tetrachloride (CCl4)-induced cirrhosis. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Western-blot, and RNA-sequencing, whereas cell proliferation was assessed by immunohistochemistry of PCNA, Western-blot, and RNA-sequencing. The results suggest that cell proliferation and cell death, as well as the balance between the two, are altered throughout the different stages of chronic liver disease and are related to changes in liver size. Prominent increases of both cell proliferation and cell death by apoptosis were observed in rats at all stages of cirrhosis compared with control rats without cirrhosis. An increase in the cell proliferation/cell death balance was associated with an increase in liver mass, whereas a decrease in the cell proliferation/cell death balance was associated with a decrease in liver size. Based on these findings, the relationship between the disease stage and changes in cell proliferation and cell death warrant further study for increasing our knowledge of the pathophysiology of the disease and for prompting new diagnostic and therapeutic approaches