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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Alanine Transaminase, Amides, Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Animals, Aspartate Aminotransferases, Benzimidazoles, Biphenyl Compounds, Cells, Cultured, Choline Deficiency, DNA Damage, Disease Models, Animal, Fatty Liver, Liver, Liver Cirrhosis, Male, Organ Size, Oxidative Stress, Protein Kinase Inhibitors, Pyridines, RNA, Messenger, Rats, Rats, Wistar, Reactive Oxygen Species, Signal Transduction, Tetrazoles, Time Factors, Tumor Necrosis Factor-alpha, rho GTP-Binding Proteins, rho-Associated Kinases.
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Is rho/Rho kinase a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis? Context: The molecular mechanisms underlying the involvement of the renin-angiotensin system in hepatic fibrosis are unclear. Recently, it was reported that a Rho kinase inhibitor prevented fibrosis of various tissues and that the Rho/Rho kinase pathway was involved in the renin-angiotensin system of vascular smooth muscle cells. In this study, the involvement of the Rho/Rho kinase pathway on angiotensin II signaling in liver fibrogenesis and generation of steatosis was investigated. Rats were fed a choline-deficient/L-amino acid-defined (CDAA) diet continuously and treated with a Rho kinase inhibitor, Y-27632, and an angiotensin II receptor blocker, TCV-116. Liver histology and hepatic stellate cell activation were analyzed. Free radical production was detected by 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine immunostaining and the expression of tumor necrosis factor-alpha was examined. Isolated hepatic stellate cells were pretreated with a Rho kinase inhibitor, Y-27632, or an angiotensin II receptor blocker, CV-11974, and stimulated with angiotensin II, and mRNA expression of transforming growth factor-beta and alpha-smooth muscle actin was analyzed. Both the angiotensin II receptor blocker and the Rho kinase inhibitor improved fibrosis and steatosis of the liver in CDAA-fed rats. The increase in the number of hepatocytes positive for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine in CDAA-fed rats was significantly prevented by the angiotensin II receptor blocker and the Rho kinase inhibitor. The levels of tumor necrosis factor-alpha mRNA in the liver of CDAA-fed rats were significantly increased and this increase was significantly inhibited by treatment with the angiotensin II receptor blocker and the Rho kinase inhibitor. mRNA expression of transforming growth factor-beta and alpha-smooth muscle actin stimulated by angiotensin II was also significantly suppressed by these two drugs.
assistant
These results suggest that the Rho/Rho kinase pathway is at least partly involved in the renin-angiotensin system and plays an important role in hepatic fibrosis and steatosis. Final Decision: yes