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Liver regeneration is due to hepatocyte hypertrophy and division

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Institute of Molecular and Cellular Biosciences
2012/08/29

Prometheus, Gustave Moreau. In Greek mythology, Prometheus gave fire to humankind, for which he was punished by Zeus. Chained to a rock, an eagle pecked out his liver every day, only for it to grow back every night. But it would be surprising if the ancient Greeks were aware of the liver’s regenerative power.

Prometheus, Gustave Moreau. (Wikimedia Commons)
In Greek mythology, Prometheus gave fire to humankind, for which he was punished by Zeus. Chained to a rock, an eagle pecked out his liver every day, only for it to grow back every night. But it would be surprising if the ancient Greeks were aware of the liver’s regenerative power.

The liver has a very high capacity for regeneration: a mouse liver recovers its original weight and function even after resection (surgical removal) of 70% of the organ. Conventional theory held that this phenomenal ability was achieved by the division of hepatocytes (liver cells), which account for a large part of the liver. However, there was no direct evidence to support this hypothesis.

A research group at the University of Tokyo’s Institute of Molecular and Cellular Biosciences, lead by Professor Atsushi Miyajima and then-Assistant Professor Yuichiro Miyaoka (now postdoctoral fellow at Gladstone Institute, UCSF, USA), has succeeded in making proteins that serve as markers in only a small portion of mouse hepatocytes, enabling detailed tracing of those cells’ activity after liver resection. Using this marking technique, they discovered that the number of hepatocyte cell divisions was far lower than expected.

In fact, before dividing, hepatocytes demonstrated hypertrophy (increase in size). Only if hypertrophy alone is insufficient will hepatocytes undergo cell division to increase their number and regenerate the liver. In addition, the researchers found that after a 70% resection, many of the roughly 30% of hepatocytes that have two cell nuclei undergo a highly characteristic form of division into single-nucleus cells to increase cell number.

As the chemical factory of the body the liver has more than 500 functions including metabolism and detoxification, and this great versatility makes it extremely difficult to create an artificial liver. Currently, the principle treatment of severe liver disease is by liver transplant. By deepening our understanding of the mechanism of liver regeneration, this research may lead to the development of safer and more efficient treatments for liver disease.

But why is it only the liver that has such great regenerative powers? Special properties, such as the hepatocyte hypertrophy proven for the first time through this research, might hold the key to that mystery.

Public Relations Division, The University of Tokyo, Azusa Minamizaki, Euan McKay.

Department release/press release (Japanese)

Paper

Yuichiro Miyaoka, Kazuki Ebato, Hidenori Kato, Satoko Arakawa, Shigeomi Shimizu, Atsushi Miyajima,
“Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration,”
Current Biology, Volume 22, Issue 13, 1166-1175, 31 May 2012. doi:10.1016/j.cub.2012.05.016
Article link

Links

Institute of Molecular and Cellular Biosciences

Laboratory of Cell Growth and Differentiation

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