TWEAK Induces Liver Progenitor Cell Proliferation
By Journal of Clinical Investigation
Aug 19, 2005, 13:51

Liver injury can occur as a result of alcohol toxicity, necrosis, or a host of other factors. When the liver is injured, it responds with progenitor cell (oval cell) proliferation in the remaining parts of the organ. The oval cells can become either liver cells or epithelial cells, and are vital for recovery from liver injury. But the regulation of oval cell expansion is not well understood.

In a study appearing online on August 18 in advance of print publication of the September 1 issue of the Journal of Clinical Investigation, Aniela Jakubowski and colleagues from Biogen report the discovery of a novel role for the TNF family member, TWEAK, as an inducer of oval cell proliferation in the liver. This is the first demonstration of a role for this cytokine in the regulation of liver progenitor cells.

Unlike other factors that can modulate the proliferation of oval cells, the researchers show that TWEAK acts selectively on oval cells with no effect on mature liver cells. They use three independent approaches: animals overexpressing TWEAK, adenoviral delivery of TWEAK, and TWEAK blocking antibodies in a model of oval cell hyperplasia.

The potential role for the TWEAK pathway in chronic human liver diseases that are accompanied by oval cell proliferation is suggested by data showing increased expression of the receptor for TWEAK in alcoholic cirrhosis and viral hepatitis. A better understanding of the molecular pathways regulating the progenitor cell response may lead to specific therapies for liver diseases.

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