The significance of hepatic stellate cells activation on small-for-size fatty liver graft injury

Abstract

Background and Objective: Fatty liver used in living donor liver transplantation (LDLT) may be more susceptible to ischemia-reperfusion injury. In this study, we aimed to investigate the significance of HSCs cell activation on small-for-size fatty liver graft injury and the underlying molecular mechanisms in a rat liver transplantation model. Materials and Methods: A rat non-arterialized orthotopic liver transplantation model using fatty liver grafts and cirrhotic recipients was used. Liver architecture and ultrastructure change related to hepatic sinusoidal injury were checked at different time points. HSCs activation was detected by immunostaining. cDNA microarray screening was employed to compare gene expression profiles among whole normal graft, whole fatty graft, small-for-size normal graft, and small-for-size fatty graft in order to identify distinct gene panel linking to small-for-size fatty liver graft injury. Results: The early and significant activation of HSCs in small-for-size fatty grafts was well correlated with progressive hepatic sinusoidal damage as well as survival rates. Among the over-expressed genes screened by cDNA microarray, Wnt4 was upregulated more than 10-fold in small-for-size fatty liver graft compared with whole fatty graft and small-for-size normal graft and the same significant change was detected at protein level. Overexpression of other Wnt family genes and their receptors were also investigated in small-for-size fatty liver grafts. Conclusions: Significant activation of HSCs in small-for-size fatty liver grafts suggests its important role in acute phase graft injury. Upregulation of Wnt4 expression in small-for-size fatty liver graft implicates a possible relationship between Wnt4 signaling pathway and HSCs activation.