Cells Involved in Liver Damage Play Dual Role as Tissue Repair Agent
UCSD scientists discovered a molecule that initially activates HSCs to regenerate liver cells.
Researchers found that immediately following liver injury, a cellular receptor, p75 neurotrophin receptor (p75NTR), involved in triggering cell death is also a necessary component of tissue repair and regeneration. They describe the mechanism by which cells associated with liver damage, or hepatic stellate cells (HSCs), are activated by p75NTR to promote repair in the liver.
The investigators looked at the molecular-cellular interface to study how tissues responded to deposition of fibrin. In studies of mice with excessive fibrin deposition in the liver, they found that p75NTR signaling promotes the initial activation of HSC, which stimulates the proliferation of new hepatic cells to replace those that have been damaged. The effects of p75NTR at late stages of HSC activation and liver disease remain to be determined.
"Many therapeutics for liver disease target HSCs in order to kill them, but our study found that their initial activity could actually be protective," points out Katerina Akassoglou, Ph.D., assistant professor at the the University of California, San Diego, department of pharmacology, where the research was undertaken.
"By identifying p75NTR as the specific molecular link between HSCs and liver regeneration, p75NTR could provide a new therapeutic target for promoting cell regeneration and repair during chronic liver disease or injury."
The study was published in the March 30 issue of Science.