MicroRNAs in mesenteric lymph and plasma during acute pancreatitis
Cherie Blenkiron1, Kathryn J Askelund, Satyanarayan T Shanbhag
1Departments of *Surgery and †Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand ‡Department of Pathology and Molecular Medicine, Wellington School of Medicine, University of Otago, Dunedin, New Zealand §Maurice Wilkins Centre for Molecular Biodiscovery; and ¶School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Objective:
To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and identify those that change with experimental acute pancreatitis (AP). To assess identified AP-associated miRNAs in patient plasma to evaluate them as clinical biomarkers of AP.
Background:
miRNAs, small non-protein-coding molecules that regulate gene expression, are present in many biological fluids. They are increasingly interesting as biomarkers of disease and as novel signaling molecules in pathogenesis.
Methods:
Affymetrix miRNA profiling was performed on ML collected from 3 groups of rats with either mild or moderate taurocholate-induced AP and sham controls. Quantitative reverse transcription-polymerase chain reaction was used to validate selected miRNAs in matched rat lymph and plasma and then measured in patients with mild or moderate AP and in healthy volunteers.
Results:
Eighty-five miRNAs were detectable in rat ML, and many were abundant in all animals irrespective of the presence of AP. Seven miRNAs, comprising miR-375, -217, -148a, -216a, -122, -214, and -138, were increased in ML from rats with AP (P < 0.01). Their abundance also altered with disease severity. miRNAs miR-217, -375, -122, and -148a were also increased in matched rat plasma samples by quantitative reverse transcription-polymerase chain reaction. In the clinical studies, plasma miR-216a was significantly increased in both mild and moderate AP.
Conclusions:
This study is the first to demonstrate both the presence of circulating miRNAs in lymph and the alteration of specific miRNAs in AP. Furthermore, these miRNAs alter in rat and human AP plasma and have potential to be explored as novel biomarkers of pancreatitis.
Insights
Researchers identified specific microRNAs (miRNAs) in lymph and blood that change during acute pancreatitis (AP). These circulating miRNAs show potential as novel biomarkers for diagnosing AP in patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Gastroenterology
Background:
- MicroRNAs (miRNAs) are small non-coding RNA molecules regulating gene expression.
- miRNAs are found in biological fluids and are investigated as disease biomarkers.
- Their role in disease pathogenesis and as signaling molecules is of growing interest.
Purpose of the Study:
- To isolate and identify microRNAs (miRNAs) in mesenteric lymph (ML) and peripheral blood.
- To determine if these miRNAs change in experimental acute pancreatitis (AP).
- To evaluate AP-associated miRNAs in patient plasma as potential clinical biomarkers.
Main Methods:
- miRNA profiling using Affymetrix arrays on rat ML from AP and control groups.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for miRNA validation in rat lymph and plasma.
- Measurement of selected miRNAs in plasma from human AP patients and healthy volunteers.
Main Results:
- Eighty-five miRNAs were detected in rat ML; seven (miR-375, -217, -148a, -216a, -122, -214, -138) were significantly increased in AP.
- Abundance of these miRNAs correlated with AP severity in rats.
- Plasma levels of miR-217, -375, -122, -148a increased in rats, and miR-216a was elevated in human AP patients.
Conclusions:
- This study first demonstrates circulating miRNAs in lymph and their alteration in AP.
- Specific miRNAs are altered in both rat and human AP plasma.
- These findings suggest potential for novel miRNA biomarkers in pancreatitis diagnosis.
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