Role of hepatic stellate cells in liver ischemia-reperfusion injury

Abstract

Liver ischemia-reperfusion injury (IRI) is a major complication of liver trauma, resection, and transplantation. IRI may lead to liver dysfunction and failure, but effective approach to address it is still lacking. To better understand the cellular and molecular mechanisms of liver IRI, functional roles of numerous cell types, including hepatocytes, Kupffer cells, neutrophils, and sinusoidal endothelial cells, have been intensively studied. In contrast, hepatic stellate cells (HSCs), which are well recognized by their essential functions in facilitating liver protection and repair, have gained less attention in their role in IRI. This review provides a comprehensive summary of the effects of HSCs on the injury stage of liver IRI and their associated molecular mechanisms. In addition, we discuss the regulation of liver repair and regeneration after IRI by HSCs. Finally, we highlight unanswered questions and future avenues of research regarding contributions of HSCs to IRI in the liver.

Keywords: Kupffer cells; hepatic stellate cells; hepatocytes; ischemia-reperfusion injury; liver; liver transplantation; neutrophils; sinusoidal endothelial cells.

Figure 1

Cellular and molecular mechanisms by which HSCs modulate liver IRI. Solid arrows indicate positively regulatory effect with supporting experiment data, whereas dash arrows indicate putative positively regulatory effect. KC, Kupffer cell; TC, T cell; HSC, hepatic stellate cell; MMPs, matrix metalloproteinases; ROCK, Rho-associated coiled-coil forming protein serine/threonine kinase; ET-1, endothelin-1.