title: MicroRNA biomarkers of pancreatic injury in a canine model.
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.
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA. Electronic address: rodney.rouse@fda.hhs.gov.
authors.forename: Rodney
authors.initials: R
authors.lastname: Rouse
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Rosenzweig
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Shea
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Knapton
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Sharron
authors.initials: S
authors.lastname: Stewart
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Chockalingam
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Zadrozny
authors.affiliation: U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA.
authors.forename: Karol
authors.initials: K
authors.lastname: Thompson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002108:Ceruletide / Q000633:toxicity; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D010195:Pancreatitis / Q000097:blood* / Q000235:genetics* / Q000473:pathology
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D002108:Ceruletide
keywords: Biomarker; Droplet digital PCR; Isomirs; MicroRNA; Pancreas; Pancreatitis; miR-148a; miR-216a; miR-216b; miR-217; miR-375