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

Koh Nakamaru, Takashi Tomiyama, Sanshiro Kobayashi, Manami Ikemune, Satoshi Tsukuda, Takashi Ito, Toshihiro Tanaka, Takashi Yamaguchi, Yugo Ando, Tsukasa Ikeura, Toshiro Fukui, Akiyoshi Nishio, Makoto Takaoka, Kazushige Uchida, Patrick S.C. Leung, M. E. Gershwin, Kazuichi Okazaki

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
JournalPancreatology
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • In situ hybridization
  • Inflammatory cell
  • Microarray
  • RT-PCR

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

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    Nakamaru, K., Tomiyama, T., Kobayashi, S., Ikemune, M., Tsukuda, S., Ito, T., Tanaka, T., Yamaguchi, T., Ando, Y., Ikeura, T., Fukui, T., Nishio, A., Takaoka, M., Uchida, K., Leung, P. S. C., Gershwin, M. E., & Okazaki, K. (Accepted/In press). Extracellular vesicles microRNA analysis in type 1 autoimmune pancreatitis: Increased expression of microRNA-21. Pancreatology. https://doi.org/10.1016/j.pan.2020.02.012