Senescence in liver cells is found by CSHL scientists to help limit acute tis...(injury. Several therapeutic mechan...)
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Several therapeutic mechanisms simultaneously engaged
Just as in liver cancer, the role of senescence in limiting fibrosis was two-pronged. "Cell-cycle arrest in the cells that generate the fibrosis places a kind of brake on the process, limiting how far it can go," Lowe explained. "We hypothesize that HSCs, when they senesce, secret less fibrogenic protein and also stimulate a process that tends to degrade proteins that are still present in a lesion." Lowe's team proposes that senescent cells accomplish this in part by increasing the activity of genes that stimulate the immune system.
Thus, just as senescent liver cells can play a role in tumor regression by stimulating an immune reaction, so can senescent HSCs in damaged liver tissue help clear the fibrosis by calling immune system killer cells to the scene of the damage. In such a scenario, "senescence is a kind of homeostatic mechanism that enables the tissue to return to its pre-damaged state," Lowe noted. "This may prove to be broadly relevant to other wound-healing processes."
Senescence overwhelmed: the lesson of chronic tissue damage
In marked contrast, separate experiments in mice that modeled chronic liver damage, such as that caused by alcoholism, chronic hepatitis, or fatty liver disease, showed that the mice produced senescent cells more rapidly than they could be "cleared." According to Lowe, this resulted in "persistent inflammation and advancing fibrosis" -- a state that can lead to cancer in some instances.
Considered together, the results of the experiments in chronic vs. acute fibrosis suggest, in the chronic instance, how fibrosis can lead to cirrhosis, a predisposing condition for the genetic mutations and other cellular transformations that cause liver cancer. But in the acute instance, the experiments suggest that future therapy designed to stimulate the immune cells that target senescent cells in fibrotic
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| Contact: Peter Tarr tarr123@gmail.com 516-367-8455 Cold Spring Harbor Laboratory Source:Eurekalert |
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