Changes in albumin, α-fetoprotein and collagen gene transcription in ccl4-induced hepatic fibrosis

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Abstract
In efforts to understand mechanisms of liver dysfunction in cirrhosis, transcription of specific genes important to liver function has been measured in the rat model of CCl4-induced hepatic fibrosis. The relative transcription rates of albumin, α-fetoprotein and pro-α1-collagen genes were studied during development of fibrosis and after fibrosis was established. During the initial phase of CCl4 administration, there was a decrease in albumin transcription associated with increased α-fetoprotein transcription, indicative of active liver regeneration. However, later during development of fibrosis, the response pattern of these genes was different, as albumin gene transcription was normal or increased and α-fetoprotein gene transcription was no longer increased. Three weeks after completion of CCl4 treatment (fully established cirrhosis), albumin genes responded normally or hypernormally to an acute regenerative stimulus, but the α-fetoprotein gene was again not measurably responsive. Pro-α1-collagen gene transcription increased during the entire fibrogenic process and remained elevated after cirrhosis was established. These studies suggest that a switch from albumin to α-fetoprotein gene transcription can serve as a marker of liver regenerative capacity, and that this process is altered during and after development of hepatic fibrosis. The fibrogenic process is also associated with elevated transcription of collagen genes.