AUTHOR=Xiang Hong , Tao Xufeng , Xia Shilin , Qu Jialin , Song Huiyi , Liu Jianjun , Shang Dong 

TITLE=Emodin Alleviates Sodium Taurocholate-Induced Pancreatic Acinar Cell Injury via MicroRNA-30a-5p-Mediated Inhibition of High-Temperature Requirement A/Transforming Growth Factor Beta 1 Inflammatory Signaling

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01488

DOI=10.3389/fimmu.2017.01488

ISSN=1664-3224

ABSTRACT=Pancreatitis is an inflammatory disease that is responsible for substantial morbidity and mortality, and it can induce pancreatic necrosis that starts within pancreatic acinar cells in severe cases. Emodin, a pleiotropic natural product isolated from the Chinese herb Rheum palmatum L., has effective anti-inflammatory activities. In this paper, we investigated the protective effects and molecular mechanism of emodin against sodium taurocholate (STC)-induced pancreatic acinar cells injury in vitro and in vivo; and the results showed that emodin could significantly alleviate STC-induced pancreatic acinar cells injury through decreasing trypsin, amylase and the release of inflammatory factors (TNF-α, IL-1β and IL-6). Also, we found that emodin could significantly down-regulate the HTRA1, IL-33, MyD88, TRAF-6 and NF-κB protein levels, but up-regulate the TGF-β1 protein level. These results indicated that emodin alleviated pancreatic acinar cells injury mainly through inhibiting HTRA1/TGF-β1 signalling pathway, and this finding was further proved by the HTRA1 overexpression experiments. In addition, the inflammatory regulator miRNA-30a-5p (miR-30a-5p) was confirmed to be a transcriptional brake that controls the HTRA1 gene through using a dual luciferase reporter assay, and it was up-regulated by emodin in pancreatic acinar cells. Furthermore, the pancreatic protective effects and anti-inflammatory activities of emodin were all abrogated with both miR-30a-5p inhibitor in vitro and miR-30a-5p antagomir in vivo. Collectively, these results demonstrate that miR-30a-5p/HTRA1 are the target of emodin-mediated attenuation of pancreatic acinar cell injury in pancreatitis, thus providing the foundation for further development of this natural product for medical therapy.