miR-148a suppresses autophagy by down-regulation of IL-6/STAT3 signaling in cerulein-induced acute pancreatitis.

Acute pancreatitis (AP) is a type of sterile inflammation of the pancreas, potentially leading to systemic inflammatory response syndrome or multiple organ failure. An emerging evidence that dysfunction of miRNA expression may alter pivotal physiological functions and lead to inflammation infiltration and complication of multiple diseases, including AP. Here, the AP model was successfully replicated using cerulein in vitro and in vivo. RT-qPCR was used to detect low expression of miR-148a in AP. This study verified that IL-6 was a direct target of miR-148a. Over-expression of miR-148a decreased the mRNA and protein levels of IL-6 by RT-qPCR and Elisa. Moreover, over-expression of miR-148a improved the pathological state of AP through H&E and MPO staining and transmission electron microscopy. After over-expressing miR-148a, Western blot and immunohistochemical method were used to confirm the reduction of autophagosomes and autolysosomes, blockade of the levels of p-STAT3, LC3-II, ATG7, ATG4c, Beclin1 and the increased p62 expression in AP. The expression of LAMP-2 was not significantly different. In addition, IL-6 and AG490, the IL-6/STAT3 signaling inhibitor, were used to verify the role of IL-6/STAT3 signaling in the regulation of miR-148a on autophagy in cerulein-induced AP in vitro and in vivo. Taken together, our findings indicate that miR-148a suppresses autophagy via regulating IL-6/STAT3 signaling in cerulein-induced AP in vitro and in vivo. The miR-148a appears to be a promising candidate for the gene therapy of AP.