Senescence in liver cells is found by CSHL scientists to help limit acute tis... (to divide uncontrollably -- the hallmark...)

Senescence in liver cells is found by CSHL scientists to help limit acute tissue damage

Date:8/21/2008

to divide uncontrollably -- the hallmark of cancer -- it was the mechanics of the linkage that surprised Lowe's team. When they activated p53 in mice with HCC, tumors receded -- and this regression was associated directly with activation of the immune system, whose killer cells were drawn to tumors to "clear" the senescent cells.

Lowe's new work, to be reported August 22 in the journal Cell, reveals something analogous that is no less surprising: senescent cells located in areas of damaged liver tissue called fibroses similarly provoke a beneficial immune reaction. This reaction, involving NK, or natural killer cells, and other components of the innate immune system, serve to limit fibrotic lesions and curtail episodes of induced acute liver damage in mice.

The role of senescence in liver fibrosis

Lowe's team studied the relation of senescence to liver disease in two very different contexts: one in which damage to liver tissue was acute and another in which the damage was chronic. These contrasting experiments served to define how senescence could help limit damage, and how, when the senescence process was overwhelmed by chronic damage to the liver, tissue damage could accelerate out of control.

In experiments designed to mimic damage caused by acute insults, the CSHL scientists administered a toxin to the murine liver and observed a consistent pattern: the death of liver cells, or hepatocytes, followed by the rise of fibrotic lesions -- part of the body's natural reaction, in mice as in humans, to tissue damage. These fibroses were specifically generated by activated stellate cells, or HSCs, that proliferated in direct response to liver cell death.

Subsequent steps were of greatest interest: "After we observed the HSC cells to proliferate intensely," Dr. Lowe said, "we found that eventually they senesced and were cleared from the liver, to protect it from an excessive fibrogenic response to acute
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Contact: Peter Tarr
tarr123@gmail.com
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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Senescence in liver cells is found by CSHL scientists to help limit acute tis...(to divide uncontrollably -- the hallmark...)