apyrase and Liver-Diseases--Alcoholic

Alcoholic liver disease caused by chronic excessive drinking has become one of the most common types of liver disease. Alcohol-induced inflammatory immune responses play a central role in the development of alcohol-associated steatohepatitis. The content and expression of ATP and P2X4 in the livers of alcoholic steatohepatitis mice are significantly increased. The content of ATP increased by 20 percent and the expression of P2X4 receptor protein was 1.3 times higher than that in the livers of normal mice. Treatment with 5-BDBD, a P2X4 receptor-specific inhibitor, significantly reduced alcohol-induced liver inflammation and lipid deposition. In RAW264.7 cell experiments, 5-BDBD inhibited the expression of P2X4 and alleviated alcohol-induced inflammation, while the CD39-specific inhibitor POM-1 reduced extracellular ATP degradation and promoted the expression of P2X4, thereby exacerbating inflammation. After treatment with 5-BDBD, P2X4 receptor protein expression decreased by 0.2 times and after treatment with POM-1, P2X4 receptor protein expression increased by 0.1 times compared to the alcohol-stimulated group. In addition, inhibition of P2X4 expression in RAW264.7 cells reduced calcium influx in RAW264.7 cells. P2X4 may induce the activation of NLRP3 inflammasomes by mediating calcium influx, thus exacerbating the inflammatory response, and inhibition of P2X4 expression can effectively block this process. Conclusion: These results suggest that the ATP-P2X4 signaling pathway promotes the inflammatory response in alcoholic steatohepatitis and that CD39 may play a protective role in regulating P2X4 expression by hydrolyzing ATP. In conclusion, the CD39 and ATP-P2X4 signaling pathways may be potential therapeutic targets for alcoholic steatohepatitis.

Topics: Adenosine Triphosphate; Animals; Antigens, CD; Apyrase; Fatty Liver, Alcoholic; Inflammasomes; Inflammation; Liver Diseases, Alcoholic; Mice; Receptors, Purinergic P2X4

Topics: 5'-Nucleotidase; Acetaldehyde; Adenosine; Adenosine Triphosphate; Animals; Antigens, CD; Apyrase; Carbon Tetrachloride; Colchicine; Cytokines; Disease Models, Animal; Ethanol; Gene Knockdown Techniques; Hepatic Stellate Cells; Humans; Liver Diseases, Alcoholic; Mice, Inbred C57BL; Primary Cell Culture; Rats; Receptor, Adenosine A2A; Receptor, Adenosine A2B; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta; Tungsten Compounds