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2017 ; 8
(ä): 1488
Nephropedia Template TP
Xiang H
; Tao X
; Xia S
; Qu J
; Song H
; Liu J
; Shang D
Front Immunol
2017[]; 8
(ä): 1488
PMID29163548
show 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.