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entiation. Kidney Int A\ -.550-555 ■ 
THE HEPATIC GROWTH RESPONSE 
Rebecca A. Taub, M.D., Associate Investigator 
The liver constitutes one of the few normally qui- 
escent tissues in the adult body that has the capacity 
to regenerate. As a result, it provides a unique multi- 
cellular, physiologically normal system in which to 
study the mitogenic response of epithelial cells. In 
the rat, following a 70% hepatectomy, the cells in 
the remaining intact lobes of the liver rapidly re- 
sume proliferation. They initiate the first round of 
DNA synthesis within 12 to 1 6 hours postsurgery 
and continue to traverse the cell cycle until the liver 
regains its initial mass in about 1 0 days, whereupon 
they again become quiescent. 
Although it is composed mainly of hepatocytes, 
the liver has a complex, multicellular architecture, 
implying that intercellular communications must 
exist during regeneration. Multiple factors, includ- 
ing circulating hormones, growth factors, and 
nervous input, participate in the regulation of 
this response, but the actual mechanism remains in- 
completely understood. 
To begin to comprehend the control of liver re- 
generation, Dr. Taub and her colleagues identified 
immediate-early growth response genes in regener- 
ating liver and insulin-treated H35 cells, a minimal- 
deviation hepatoma cell line that has many proper- 
ties of regenerating liver. Of the 70 total and 41 
novel immediate-early genes the laboratory identi- 
fied, those that fall into one of four categories are 
being analyzed in detail: 1) novel transcription fac- 
tor genes, 2) potential growth factor genes, 3) liver- 
specific immediate-early genes, and 4) genes with 
abnormal expression in H35 cells compared to re- 
generating liver. 
The Induction Patterns of 70 Genes 
Posthepatectomy Define the Temporal 
Course of Liver Regeneration 
While the proteins encoded by immediate-early 
and delayed-early genes are expected to have impor- 
tant roles during regeneration in regulating progres- 
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