MicroRNA biomarkers of pancreatic injury in a canine model

Exp Toxicol Pathol. 2017 Jan;69(1):33-43. doi: 10.1016/j.etp.2016.11.001. Epub 2016 Nov 17.

Abstract

Pancreas-enriched microRNAs have been experimentally investigated in rodents as candidate serum biomarkers of pancreatic injury with several different acute pancreatic injury models. In the present study, temporal and magnitude responses of exocrine pancreas-enriched miR-216a, miR-216b, and miR-217 and endocrine-enriched miR-375 and miR-148a were measured by droplet digital PCR in serum in a caerulein model of pancreatic injury in the dog. All 5 microRNAs followed a similar time course that mirrored the responses of the conventional serum pancreatic injury biomarkers, amylase and lipase. Detection was improved through the use of assays designed against microRNA isomers (isomirs) identified by sequencing. Serum biomarker increases were concordant with histopathology defined acinar cell injury. Minimal islet cell changes were noted. The pancreas-enriched microRNAs demonstrated similar or greater sensitivity, a larger range of response, and a higher correlation to acinar cell injury compared to amylase and lipase. Our results further support the translational potential of pancreas-enriched microRNAs as sensitive biomarkers of acinar cell injury with evidence from an additional non-clinical model system.

Keywords: Biomarker; Droplet digital PCR; Isomirs; MicroRNA; Pancreas; Pancreatitis; miR-148a; miR-216a; miR-216b; miR-217; miR-375.

MeSH terms

  • Animals
  • Biomarkers / blood*
  • Ceruletide / toxicity
  • Disease Models, Animal
  • Dogs
  • Male
  • MicroRNAs / blood*
  • Pancreatitis / blood*
  • Pancreatitis / genetics*
  • Pancreatitis / pathology

Substances

  • Biomarkers
  • MicroRNAs
  • Ceruletide