The dynamics of microRNAs level associated with pathological venous angiogenesis in experimental toxic liver fibrosis in rats

Abstract

BACKGROUND: It is known that miRNAs are important in liver fibrogenesis. Studies regarding the role of miRNAs in pathological angiogenesis and sinusoid capillarization are insufficient. AIM: to study the molecular targets (miRNAs and mRNAs) dynamics of associated with pathological angiogenesis in toxic fibrosis of the liver; to evaluate the relationship of the selected molecular factors to the processes of restructuring the intrahepatic vascular system. METHODS: Fibrosis and subsequent cirrhosis of the liver in rats of the Wistar line (males) were induced for 17 weeks by a freshly prepared solution of thioacetamide. The level of miRNA-19а-3р, miRNA-29b-3р, miRNA-29b-1-5p, miRNA-34b-5р, miRNA-125b-5р, miRNA-130a-5p, miRNA-195-5р, miRNA-449а-5р, miRNA-449с-5р, miRNA-466d, miRNA-489-3р, miRNA-495, miRNA-664-3р, miRNA-3085, miRNA-3558-3р in fresh frozen liver samples, was determined by Two-tailed RT-qPCR. RESULTS: A change in the profile of targeted miRNAs was established during the initiation and progression of toxic fibrosis. The statistically significant decrease in the level of the miRNA-195-5p and miRNA-664-3p is registered compared to the control point 3 weeks of the experiment, as well as a symmetrical decrease in the level of Vegfa and Ang genes. An increase in the amount of veins is associated with a decrease in the level of miRNA-3585-3p and mRNA Cxcl12, as well as an increase in the area of cells CK19+ in the bile ducts. CONCLUSION: A joint analysis of morphological and molecular parameters allowed us to suggest that pathological angiogenesis in the toxic model of fibrosis does not proceed the same for arteries, veins and sinusoids. At the same time, Vegfa is probably involved in venous angiogenesis. Despite the decrease in the mRNA level compared to the control point, starting at the stage of portal fibrosis (3 weeks of experiment), its partial recovery, statistically significant increase and correlation with an increase in the amount of veins is observed. Perhaps, against the background of general depression of the synthesis of mRNA with the development of toxic fibrosis, the level of the Vegfa mRNA remains sufficient to stimulate pathological venous angiogenesis. The dynamics of mRNA Ang can be associated with the angiogenesis of the arteries and the capillarization of sinusoids.