Researchers identify critical receptor in liver regeneration

In studies in mouse models, researchers at the University of California, San Diego (UCSD) School of Medicine have found that a cellular receptor involved in triggering cell death is also a necessary component of tissue repair and regeneration immediately following liver injury. This discovery could have implications for early intervention or therapy in liver disease such as cirrhosis or hepatitis.

In a report to be published in the March 30 issue of the journal Science, Katerina Akassoglou, Ph.D. assistant professor in UCSD's Department of Pharmacology, and colleagues describe the mechanism by which cells associated with liver damage, called hepatic stellate cells (HSCs), are activated by a cell surface molecule called the p75 neurotrophin receptor (p75NTR) to promote repair in the liver.

"Many therapeutics for liver disease target HSCs in order to kill them, but our study in animal models found that their initial activity could actually be protective," said Akassoglou.

When chronic liver injury occurs, cells in the liver begin producing collagen and other proteins that lead to the formation of fibrous tissue and scarring. Akassoglou's team looked at the molecular-cellular interface to discover how tissues respond to deposition of the fibrous protein, fibrin. In studies of a mouse model with excessive fibrin deposition in the liver, the researchers 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.

"We were intrigued by the increase of p75NTR expression after liver injury and hypothesized that p75NTR might regulate the progression of liver disease," said Akassoglou. "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."

This discovery suggests the importance of sustaining p75 and early HSC activation – for example, in the case of liver transplantation when regeneration of liver cells is critical.

Source: University of California - San Diego

Related stories:

Structure of key epigenetics component identified
Scientists from the Structural Genomics Consortium (SGC) have determined the 3D structure of a key protein component involved in enabling "epigenetic code" to be copied accurately from cell to cell.
Gene is likely cause of stroke-inducing vascular malformations
UCSF scientists have discovered that a gene controlling whether blood vessels differentiate into arteries or veins during embryonic development is linked to a vascular disorder in the brain that causes stroke.
Noninvasive test accurately identifies advanced liver disease without biopsy
Non-invasively measuring liver stiffness with transient elastography accurately diagnoses patients with late-stage liver disease, reports a new study in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute.
New approach, old drug show promise against hepatitis C, research shows
The fight against the liver disease hepatitis C has been at something of an impasse for years, with more than 150 million people currently infected, and traditional antiviral treatments causing nasty side effects and often falling short of a cure. Using a novel technique, medical and engineering researchers at Stanford University have discovered a vulnerable step in the virus' reproduction process that in lab testing could be effectively targeted with an obsolete antihistamine.
Memory trick shows brain organization
A simple memory trick has helped show UC Davis researchers how an area of the brain called the perirhinal cortex can contribute to forming memories. The finding expands our understanding of how those brain areas that form memories are organized.
Study: 12 percent of Indian deaths due to alcohol
(AP) -- Almost 12 percent of the deaths among American Indians and Alaska Natives are alcohol-related - more than three times the percentage in the general population, a new federal report says.
High levels of uric acid may be associated with high blood pressure
Reducing levels of uric acid in blood lowered blood pressure to normal in most teens in a study designed to investigate a possible link between blood pressure and the chemical, a waste product of the body's normal metabolism, said researchers at Baylor College of Medicine in a report that appears in the current issue of the Journal of the American Medical Association.
FDA investigates possible Vytorin link to cancer
(AP) -- Federal drug safety regulators said Thursday they are investigating whether the cholesterol-lowering drug Vytorin can increase patients' risk of developing cancer.

News discussion:

Medicine & Health news