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10.3389/fimmu.2017.01488

http://scihub22266oqcxt.onion/10.3389/fimmu.2017.01488
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suck abstract from ncbi


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pmid29163548      Front+Immunol 2017 ; 8 (ä): ä
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  • 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 #MMPMID29163548
  • Xiang H; Tao X; Xia S; Qu J; Song H; Liu J; Shang D
  • Front Immunol 2017[]; 8 (ä): ä PMID29163548show ga
  • 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 (tumor necrosis factor alpha, interleukin-1?, and interleukin-6). Also, we found that emodin could significantly downregulate the HTRA1, interleukin-33, myeloid differentiation primary response gene 88, TNF receptor-associated factor-6, and nuclear factor kappa-B protein levels, but upregulate the transforming growth factor beta 1 (TGF-?1) protein level. These results indicated that emodin alleviated pancreatic acinar cells injury mainly through inhibiting HTRA1/TGF-?1 signaling pathway, and this finding was further proved by the HTRA1 overexpression experiments. In addition, the inflammatory regulator microRNA-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 upregulated 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.
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