TUESDAY, Dec. 22 (HealthDay News) -- Deletion of a cellular signaling protein specifically in hepatocytes leads to hepatocyte death and compensatory liver damage and cancer, according to a study published online Dec. 18 in the Proceedings of the National Academy of Sciences.
To investigate the role of TAK1, which has been implicated in both cell death and carcinogenesis in the liver, Sayaka Inokuchi, from the University of California San Diego in La Jolla, and colleagues generated mice lacking the Tak1 gene in hepatocytes.
The researchers found that the mice had high levels of spontaneous hepatocyte death, leading to compensatory proliferation, inflammation and fibrosis at only 1 month of age. The mice developed liver tumors starting at 4 months of age, and markers expressed by the tumors suggested that the tumors were potentially malignant. This appeared to be partially due to tumor necrosis factor, since deletion of tumor necrosis factor receptor type I reduced the liver damage, inflammation and fibrosis.
"In conclusion, hepatocyte-specific deletion of TAK1 in mice resulted in spontaneous hepatocyte death, inflammation, fibrosis, and carcinogenesis that was partially mediated by TNFR signaling, indicating that TAK1 is an essential component for cellular homeostasis in the liver," Inokuchi and colleagues write.
Abstract
Full Text (subscription or payment may be required)
