SerpinB3 administration protects liver against ischemia-reperfusion injury

Abstract

We have investigated the change in SerpinB3 during hepatic ischemia and the potential role of its antiprotease activity in cell protection by the administration of wild-type SerpinB3 (SerpinB3-WT) or active loop-deleted recombinant SerpinB3 protein (SerpinB3-D) in a rat model of ischemia (60 min)/reperfusion (60 min) (I/R). A time-dependent increase of SerpinB3, both at transcription and protein level, was found in ischemic livers after 60, 120 and 180 min. SerpinB3-WT decreased polymorphonuclear cell infiltration and serum enzymes and increased ATP when compared with I/R group. These events were not obtained using SerpinB3-D. No significant changes in both liver SerpinB3 mRNA and protein were found in all I/R groups considered. The present data show that the administration of SerpinB3-WT reduced the I/R injury and this effect appears to be dependent on its anti-protease activity.

SERPINB3 in fibrogenic chronic liver diseases and primary liver cancers

“…Strategies by which SERPINB3 leads to the development of primary liver cancers are multiple and are supported by the previously described findings, including apoptosis resistance, increased proliferation and EMT induction, impaired immune response, and induction of stemness features. While these properties confer cell protection in acute damage conditions [126][127][128], they favor malignant transformation in case of chronic injuries. It is worth noting that SERPINB3 has been detected in the more aggressive forms of all the types of primary liver cancers, including HCC, cholangiocarcinoma, and hepatoblastoma and this is not surprising, considering that this SERPIN is expressed in the hepatic stem cells compartment, consisting in the epithelial cell adhesion molecule (EpCAM) positive fraction, sorted from both foetal and adult cirrhotic livers [129].…”

Fatty Acids and Bilirubin as Intrinsic Autofluorescence Serum Biomarkers of Drug Action in a Rat Model of Liver Ischemia and Reperfusion

“…Soon after, the abdomen was opened by a median incision and ischemia of liver left and median lobes was induced by clamping the portal vein and hepatic artery with microvascular clips. Sixty minutes later the microvascular clips were removed to allow liver blood reperfusion for 60 min [71,72]. To prevent heat loss during these procedures, the rats were placed on a warm support stand.…”