Abnormal Distribution and Upregulation of Tenascin-C mRNA Expression in the Liver of 90% Hepatectomy Rats are Related to Post-hepatectomy Liver Failure.

Background: Post-hepatectomy liver failure (PHLF) is the most serious complication after extended hepatectomy, with a high perioperative mortality rate. Matricellular protein tenascin-C (TNC) has been related to blood flow change and inflammation. We aimed to explore the hepatic changes of TNC and its relationship with PHLF. Materials and Methods: Rats were divided into seven groups: Sham operation, 90% partial hepatectomy (90PH) as a PHLF model, 85% (85PH), and 68% (68PH) hepatectomy without or with lipopolysaccharide (LPS) treatment. The distribution of TNC protein, the mRNA expression of TNC and other endothelial response genes, and the cellular TNC located in the rat livers were evaluated by immunostaining, quantitative real-time polymerase chain reaction, and RNAscope assay. Results: TNC mRNA in the liver tissue was significantly upregulated after hepatectomy and reached the highest level in the 90PH rats compared with those in the 85PH and 68PH rats. This upregulation was closely correlated with the changes of severe liver injury, inhibited liver regeneration, and upregulation of KLF2, ET-1, eNOS, and TM-1 in 90PH rat livers. We found a robust disturbance of hepatic TNC protein distribution in 90PH rat livers with an obvious reduction in hepatic sinusoids but an increase around large blood vessels, which were consistent with the severe liver injury of the 90PH rats. It was also found for the first time that treatment with the endotoxin LPS tremendously exacerbated the above changes of TNC. Conclusion: The distribution and expression of TNC mRNA changed dramatically and contributed to the occurrence of PHLF.