MicroRNA biomarkers of pancreatic injury in a canine model

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• 作者：Rodney Rouse ; ^{rodney.rouse@fda.hhs.gov} ; Barry Rosenzweig ; Katie Shea ; Alan Knapton ; Sharron Stewart ; Lin Xu ; Ashok Chockalingam ; Leah Zadrozny ; Karol Thompson
• 关键词：Biomarker ; MicroRNA ; Pancreas ; Pancreatitis ; miR-216a ; miR-216b ; miR-217 ; miR-375 ; miR-148a ; Droplet digital PCR ; Isomirs
• 刊名：Experimental and Toxicologic Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：69
• 期：1
• 页码：33-43
• 全文大小：2476 K
• 卷排序：69

文摘

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.