Evaluation of Circulating MicroRNA Biomarkers in the Acute Pancreatic Injury Dog Model

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.

Serum microRNAs as novel biomarkers for early prediction of disease severity in patients with acute pancreatitis

“…Lee Hb et al have shown that miR-216a and miR-375 could predict the degree of pancreatic injury in dog model [11].Furthermore, some studies focused on serum miRNAs profiles of SAP patients with a specific organ failure [12,13]. Notably, the miRNAs profile in the present study was quite different from those reported by others [6,[9][10][11][12][13]. One possible reason is that the classifications of enrolled patients were different.…”

“…An overexpression of miR-155 has been reported to be correlated with SAP [9], but it was also demonstrated to be inversely correlated with SAP in another study [10]. Lee Hb et al have shown that miR-216a and miR-375 could predict the degree of pancreatic injury in dog model [11].Furthermore, some studies focused on serum miRNAs profiles of SAP patients with a specific organ failure [12,13]. Notably, the miRNAs profile in the present study was quite different from those reported by others [6,[9][10][11][12][13].…”

MicroRNAs as systemic biomarkers to assess distress in animal models for gastrointestinal diseases

“…These results indicate that miR-132 might function as a good biomarker to assess distress in gastrointestinal animal models, whereas miR-375, miR-30b and miR-203 might be biomarkers indicating disease-specific pathophysiological processes. For example, miR-375 was specifically induced during pancreatitis and this miRNA is known to be upregulated in patients and animals bearing chronic pancreatitis and might, therefore, reflect the degree of the pancreatic injury [31][32][33][34] . After BDL miR-375 expression was significantly downregulated.…”

MicroRNAs in acute pancreatitis: From pathogenesis to novel diagnosis and therapy

“…Exogenous reference genes (Kong et al, 2010) miR-216a, miR-216b, and miR-375 Up SD rats L-arg Plasma Exogenous reference genes (Endo et al, 2013) miR-375, miR-217, miR-148a, and miR-122 (Lee et al, 2018) miR-216a and miR-217 Up C57BL6 mice and SD rats Caerulein, L-arg, or ligation of pancreatic duct Serum U6 (Goodwin et al, 2014) miR-216a and miR-217 Up C57BL6 mice and SD rats Caerulein or cyanohydroxybutene Serum Not mentioned (Wang et al, 2017) miR-216a, miR-216a, miR-375, and miR-217 Up SD rats Caerulein Serum Exogenous reference genes (Calvano et al, 2016) Abbreviations: AP, acute pancreatitis; miRNAs/miR, microRNAs. YANG ET AL.…”