Background & aims: MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate gene expression by binding to the 3' untranslated region (UTR) of target mRNAs and can be applied in gene therapy. Acute pancreatitis is an inflammatory pancreatic disease that carries considerable morbidity and mortality. The purpose of this study was to explore the therapeutic potential of microRNA-141 (miR-141) for acute pancreatitis in vivo.
Methods: AP was induced by two hourly intra-peritoneal (i.p.) injections of l-arginine (200mg × 2/100 g.BW). Control mice received normal saline injections. In a separate group, normal saline, empty adenoviral vector and miR-141 adenoviral vector were given to the mice via tail vein hydrodynamically at 72 h before the first l-arginine injection. All the mice were euthanized at 24 h after the last l-arginine injection, and the pancreatic tissues were assessed by qRT-PCR, Western blotting and electron microscopy.
Results: miR-141 directly inhibited HMGB1 expression in mouse hepal-6 cell. Furthermore, systemic administration of the miR-141 knock-down the expression of HMGB1 protein and further antagonized the downstream protein Beclin-1, leading to the reduction of autophagosomes and autolysosomes, blockade of the LC3-II level and the increased levels of p62 protein after injection of l-arginine. In addition, the level of Lamp-2 was not significantly different.
Conclusions: For the first time miR-141 was applied in acute pancreatitis treatment in vivo. Inhibition of HMGB1 by miR-141 may block the process of autophagosome formation through the HMGB1/Beclin-1 pathway. The miR-141 appears to be a promising candidate for the gene therapy of acute pancreatitis.
Keywords: Acute pancreatitis; Autophagy; Gene therapy; microRNA-141.
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