Abstract
This study aimed to evaluate the usefulness of four microRNAs (miRNAs) in an acute pancreatic injury dog model. Acute pancreatitis was induced by infusion of cerulein for 2 h (7.5 μg/kg/h). The levels of well-known miRNAs, microRNA-216a (miR-216a) and microRNA-375 (miR-375), and new candidates microRNA-551b (miR-551b), and microRNA-7 (miR-7), were measured at 0, 0.5, 1, 2, 6, 12, and 24 h with serum amylase and lipase, and histopathological examination was performed. Among the four miRNAs, miR-216a and miR-375, and serum enzymes were significantly increased by cerulein treatment. The expression levels of miRNAs and serum enzymes peaked at 2–6 h with a similar pattern; however, the overall increases in miR-216a and miR-375 levels were much higher than those of the serum enzyme biomarkers. Increased levels of miR-216a and miR-375 were most highly correlated to the degree of individual histopathological injuries of the pancreas, and showed much greater dynamic response than serum enzyme biomarkers. Twenty-four-hour time-course analysis in this study revealed time-dependent changes of miRNA expression levels, from initial increase to decrease by predose level in acute pancreatitis. Our findings demonstrate that, in dogs, miR-216a and miR-375 have the potential to sensitively detect pancreatitis and reflect well the degree of pancreatic injury, whereas miR-551b and miR-7 do not.
Highlights
Some commonly prescribed medications are associated with drug-induced pancreatic injury, and mortality reaches 30% in patients with severe pancreatitis in serious cases [1,2]
Circulating miR-216a was detectable in all patients with acute pancreatitis; the ability of this miRNA to differentiate between moderate and severe pancreatic damage was inconsistent [16,17]
We evaluate the fluctuations of four selected miRNAs compared with serum pancreatic injury biomarkers, amylase and lipase, in a beagle dog pancreatitis model
Summary
Some commonly prescribed medications are associated with drug-induced pancreatic injury, and mortality reaches 30% in patients with severe pancreatitis in serious cases [1,2]. Circulating miR-216a was detectable in all patients with acute pancreatitis; the ability of this miRNA to differentiate between moderate and severe pancreatic damage was inconsistent [16,17] In addition to these well-known miRNAs, two new candidate miRNA biomarkers of pancreatic damage have been identified in humans. We evaluate the fluctuations of four selected miRNAs compared with serum pancreatic injury biomarkers, amylase and lipase, in a beagle dog pancreatitis model. The objectives of this study were to examine the levels of two well-known miRNAs, miR-216a and miR-375, and two new candidate miRNAs, miR-551b and miR-7, and evaluate their usefulness as potential biomarkers for acute pancreatic injury in preclinical studies. We compared the levels of these miRNAs with those of serum amylase and lipase, the conventional biomarkers of pancreatic injury, and assessed concordance of the results with histopathological analyses of the pancreas to evaluate the superiority of miRNAs as candidate biomarkers
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