Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
Pancreatology. 2020 Apr;20(3):318-324. doi: 10.1016/j.pan.2020.02.012. Epub 2020 Feb 21.
The 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.
EV 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.
Signals 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).
Circulating 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.
1 型自身免疫性胰腺炎（AIP）的分子基础仍不清楚。最近，人们对细胞外囊泡 microRNA（EV miRNA）在免疫稳态中的作用给予了关注，这促使我们对 AIP 患者血清来源的 EV 进行了广泛的 miRNA 筛选。
使用微阵列分析 AIP、慢性胰腺炎（CP）和健康成人（HC）样本中的 EV miRNA（每组 10 例）。信号差异>3 倍或<1/3 倍表示表达差异显著。对另一个 AIP（n=14）、CP（n=10）和 HC（n=10）样本的 EV miRNA 进行了逆转录聚合酶链反应（RT-PCR）分析。使用原位杂交（ISH）在每组另外 3 例中评估胰腺组织中的 miRNA 表达。
与 HC 相比，AIP 样本中 8 种 miRNA（miR-659-3p、-27a-3p、-99a-5p、-21-5p、-205-5p、-100-5p、-29c-3p 和-125b-1-3p）的信号显著升高，而 miR-4252 和 -5004-5p 的信号显著降低。AIP 患者的 EV miR-21-5p 明显高于 HC（P=0.035）和 CP（P=0.048）。AIP 患者中 miR-21-5p 阳性炎症细胞的数量明显高于 CP（P=0.014）。
与 HC 和 CP 相比，AIP 患者的循环 EV 表现出改变的 miRNA 表达模式，其中 miR-21-5p 升高。miR-21-5p 在 AIP 的胰腺炎症细胞中高度表达。我们的数据表明，miR-21-5p 可能参与 AIP 病理生理学中效应途径的调节，从而将 AIP 与 CP 区分开来。
