Hepatic Stellate Cell Behavior during Resolution of Liver Injury

ABSTRACT

Acute self-limiting and chronic liver injury are both associated with activation and proliferation of hepatic stellate cells (HSCs). In chronic injury, activated stellate cells are the major source of the collagens that comprise fibrosis and cirrhosis, as well as of the tissue inhibitors of metalloproteinases (TIMPs) which inhibit collagen degradation. Recovery from acute and chronic injury is characterized by apoptosis of activated HSCs, which removes extracellular matrix-producing cells that are also expressing TIMPs, thereby relieving the inhibition of matrix degradation. HSC apoptosis is regulated in progressive injury and counterbalances cell proliferation. Apoptosis probably also represents a default pathway for the HSCs. The survival of activated HSCs in liver injury is dependent on soluble growth factors and cytokines, and on components of the fibrotic matrix. Additionally, stimulation of death receptors expressed on HSCs can precipitate their apoptosis. Our increasing understanding of the process of stellate cell behavior in recovery from injury is likely to be important to the design of antifibrotic therapies.

KEYWORD

Hepatic stellate cell - apoptosis - death receptor - liver fibrosis - matrix degradation

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