RNA sequence analysis reveals pathways and candidate genes associated with liver injury in a rat pancreatitis model.

BACKGROUND

The morbidity and mortality associated with acute pancreatitis (AP) are largely attributable to abnormalities that occur in distant organs, such as liver and lungs. Pancreatitis-associated liver injury (PALI) remains a serious and even fatal complication during the progression of AP. However, the exact pathophysiological mechanism is still unclear.

METHODS

In the present study, we used, for the first time, RNA-seq method to reveal pathways and candidate genes associated with PALI in rats. AP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. The RNA-seq results of selected genes were validated by RT-PCR and immunohistochemistry assay.

RESULTS

GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis indicated that Toll like receptor 4 (TLR4) signaling pathway and transforming growth factor β1 (TGF-β1) and p38 mitogen-activated protein kinase (MAPK) signaling pathway (TGF-β1-p38 MAPK) were involved in the course of PALI. In addition, other factors were also found to be involved in the course of PALI, such as the decreased antioxidant activity, excessive production of inflammatory mediators and alterations in liver metabolism.

CONCLUSIONS

The study sheds some new insight on our understanding of the pathophysiology of PALI and provides some clues to the identification of potential therapeutic targets.