Featured Research

from universities, journals, and other organizations

To Protect Against Liver Disease, Body Puts Cells 'Under Arrest'

Date:
August 22, 2008
Source:
Cell Press
Summary:
A stable form of cell-cycle arrest known to offer potent protection against cancer also limits liver fibrosis, a condition characterized by an excess of fibrous tissue, according to a new report.

A stable form of cell-cycle arrest known to offer potent protection against cancer also limits liver fibrosis, a condition characterized by an excess of fibrous tissue, according to a new report in the August 22nd Cell, a Cell Press publication. Triggered by chronic liver damage produced by hepatitis infection, alcohol abuse, or fatty liver disease, liver fibrosis can lead to cirrhosis, a major health problem worldwide and the 12th most common cause of death in the United States.

Related Articles


The new findings may have important implications for treating cirrhosis, a disease now considered to be irreversible. It could offer new insight into other disease states as well.

"Fibrosis is a disease of many organs—lungs, kidneys, pancreas, prostate, skin," said Valery Krizhanovsky of Cold Spring Harbor Laboratory. "It's possible this mechanism in the liver is relevant to fibrotic situations in other tissues."

The state of cell-cycle arrest known as senescence was first described decades ago, but the phenomenon was thought to occur only in cultured cells in the laboratory, Krizhanovsky explained. More recent studies found that cellular senescence helps protect against the formation of tumors and aids in the response to certain anticancer agents.

Interestingly, the researchers said, senescent cells had also been observed in some aged or damaged tissues, including the cirrhotic livers of human patients. However, the functional contribution of cellular senescence to diseases other than cancer hadn't been examined.

To study the potential role of senescence in liver cirrhosis, the researchers examined mice treated with a liver-damaging agent. They found that senescent cells accumulated in the livers of the mice, derived primarily from activated stellate cells. Stellate cells are those that initially proliferate in response to liver damage and are responsible for producing the extracellular matrix—a kind of structural support for cells—that is the hallmark of fibrotic scars.

"Once a lot of extracellular matrix has formed, it's very hard to clear," Krizhanovsky explained. "The material just sits there and creates an inflammatory environment."

Their new findings offer some hope, however. The senescent stellate cells showed signs of reduced secretion of extracellular matrix components, enhanced secretion of enzymes that degrade extracellular matrix, and enhanced immune surveillance. Accordingly natural killer cells preferentially target senescent-activated stellate cells both in cell culture and in living animals, they found, helping to resolve fibrosis. On the other hand, stellate cells continued to divide in mice lacking key components of the senescence program, leading to excessive liver fibrosis.

The results suggest that immunostimulatory therapies might enhance senescent cell clearance and should be tested for the potential treatment of patients with liver fibrosis, especially in its early stages or following short-term exposure to liver toxins.

"We suggest that, following tissue damage, hepatic stellate cells become activated and proliferate intensely, senesce, and are eventually cleared to protect the liver from an excessive fibrogenic response to acute injury," the researchers concluded. "However, in response to chronic tissue damage, for example, as produced by viral hepatitis or fatty liver disease, continual rounds of hepatocyte [i.e. liver cell] death and stellate cell proliferation allow the production of senescent cells to outpace their clearance, contributing to persistent inflammation and advancing fibrosis. Such a state, while initially beneficial, may eventually trigger the aberrant proliferation and transformation of damaged hepatocytes, leading to cancer. "

In fact, Krizhanovsky noted, cirrhosis is the main risk factor for developing an often fatal form of liver cancer known as hepatocellular carcinoma.

The researchers include Valery Krizhanovsky, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; Monica Yon, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; Departamento de Imunologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo and Instituto de Investigacao em Imunologia, Instituto do Milenio, Brazil; Ross A. Dickins, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; Stephen Hearn, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; Janelle Simon, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, Howard Hughes Medical Institute, Cold Spring Harbor, NY; Cornelius Miething, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; Herman Yee, New York University School of Medicine, New York, NY; Lars Zender, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; and Scott W. Lowe, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, Howard Hughes Medical Institute, Cold Spring Harbor, NY.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "To Protect Against Liver Disease, Body Puts Cells 'Under Arrest'." ScienceDaily. ScienceDaily, 22 August 2008. <www.sciencedaily.com/releases/2008/08/080821163852.htm>.
Cell Press. (2008, August 22). To Protect Against Liver Disease, Body Puts Cells 'Under Arrest'. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2008/08/080821163852.htm
Cell Press. "To Protect Against Liver Disease, Body Puts Cells 'Under Arrest'." ScienceDaily. www.sciencedaily.com/releases/2008/08/080821163852.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins