Adenovirus-mediated artificial miRNA targetting fibrinogen-like protein 2 attenuates the severity of acute pancreatitis in mice

Biosci Rep. 2017 Nov 23;37(6):BSR20170964. doi: 10.1042/BSR20170964. Print 2017 Dec 22.


Severe acute pancreatitis (SAP) remains to be challenging for its unpredictable inflammatory progression from acute pancreatitis to SAP. Apoptosis is an important pathology of SAP. Fibrinogen-like protein 2 (FGL2) has been reported to be involved in apoptosis. The present study aimed to explore the therapeutic effect of an adenovirus-mediated artificial miRNA targetting FGL2 (Ad-FGL2-miRNA) in taurocholate-induced murine pancreatitis models. Sodium taurocholate was retrogradely injected into the biliopancreatic ducts of the C57/BL mice to induce SAP. FGL2 expression was measured with reverse transcription-PCR, Western blotting, and immunohistochemical staining. ELISA was used to detect the activity of amylase and the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In addition, the mRNA levels of TNF-α and IL-1β were also detected. Finally, apoptosis was assessed by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) method and Western blotting. Ad-FGL2-miRNA significantly suppressed FGL2 expression and alleviated pancreatic injury. Also, Ad-FGL2-miRNA markedly inhibited a post-SAP increase in the activation of TNF-α and IL-1β. Finally, pretreatment with Ad-FGL2-miRNA ameliorated apoptosis at the early stage of SAP by modulating cleaved caspase-3 and therefore played a protective role. These results indicated that FGL2 might be a promising target for attenuating the severity of SAP and adenovirus-mediated artificial miRNAs targetting FGL2 represented a potential therapeutic approach for the treatment of SAP.

Keywords: acute pancreatitis; apoptosis; fibrinogen-like protein 2; molecular mechanism.

MeSH terms

  • Adenoviridae
  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Fibrinogen / genetics
  • Fibrinogen / metabolism*
  • Genetic Therapy
  • HEK293 Cells
  • Humans
  • Interleukin-1beta / analysis
  • Interleukin-1beta / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pancreatitis / chemically induced
  • Pancreatitis / therapy*
  • Taurocholic Acid / pharmacology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / drug effects


  • Fgl2 protein, mouse
  • Interleukin-1beta
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Taurocholic Acid
  • Fibrinogen
  • Casp3 protein, mouse
  • Caspase 3