Abstract
To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and identify those that change with experimental acute pancreatitis (AP). To assess identified AP-associated miRNAs in patient plasma to evaluate them as clinical biomarkers of AP.
miRNAs, small non-protein-coding molecules that regulate gene expression, are present in many biological fluids. They are increasingly interesting as biomarkers of disease and as novel signaling molecules in pathogenesis.
Affymetrix miRNA profiling was performed on ML collected from 3 groups of rats with either mild or moderate taurocholate-induced AP and sham controls. Quantitative reverse transcription-polymerase chain reaction was used to validate selected miRNAs in matched rat lymph and plasma and then measured in patients with mild or moderate AP and in healthy volunteers.
Eighty-five miRNAs were detectable in rat ML, and many were abundant in all animals irrespective of the presence of AP. Seven miRNAs, comprising miR-375, -217, -148a, -216a, -122, -214, and -138, were increased in ML from rats with AP (P < 0.01). Their abundance also altered with disease severity. miRNAs miR-217, -375, -122, and -148a were also increased in matched rat plasma samples by quantitative reverse transcription-polymerase chain reaction. In the clinical studies, plasma miR-216a was significantly increased in both mild and moderate AP.
This study is the first to demonstrate both the presence of circulating miRNAs in lymph and the alteration of specific miRNAs in AP. Furthermore, these miRNAs alter in rat and human AP plasma and have potential to be explored as novel biomarkers of pancreatitis.