Extracellular vesicles microRNA analysis in type 1 autoimmune pancreatitis: Increased expression of microRNA-21

Abstract

BackgroundThe molecular basis of type 1 autoimmune pancreatitis (AIP) remains unclear. Recent attention on the role of extracellular vesicles microRNA (EV miRNA) in immune homeostasis has prompted us to perform an extensive miRNA screening of serum-derived EV in AIP. MethodsEV miRNA expression was analyzed using microarrays in AIP, chronic pancreatitis (CP), and healthy adult (HC) samples (n = 10 from each group). Differences in signals, > 3 or <1/3 times, represented significant differences in expression. Another cohort of AIP (n = 14), CP (n = 10), and HC (n = 10) samples of EV miRNA was analyzed using reverse-transcription polymerase chain reaction (RT-PCR). miRNA expression in pancreatic tissues was evaluated using in situ hybridization (ISH) in three additional subjects from each group. ResultsSignals of eight miRNAs (miR-659–3p, −27a-3p, −99a-5p, -21–5p, -205–5p, -100–5p, −29c-3p, and −125b-1-3p) were significantly higher, while those of two miRNAs (miR-4252 and -5004–5p) were significantly lower in AIP than in HC. EV miR-21–5p was significantly up-regulated in AIP than in HC (P = 0.035) and CP (P = 0.048). The number of miR-21–5p positive inflammatory cells was significantly elevated in AIP than in CP (P = 0.014). ConclusionsCirculating EVs exhibited altered miRNA expression patterns with elevated miR-21–5p in AIP when compared with those in HC and CP. miR-21–5p was highly expressed in pancreatic inflammatory cells in AIP. Our data suggests that miR-21–5p may be involved in the regulation of effector pathways in the pathophysiology of AIP, thus differentiating AIP from CP.