Antischistosomiasis Liver Fibrosis Effects of Chlorogenic Acid through IL-13/miR-21/Smad7 Signaling Interactions In Vivo and In Vitro

作者：Yao, Wang; Fan, Yang; Jun, Xue; Xuan, Zhou; Lei, Luo; Qian, Ma; Yun-Fei, Chen; Juan, Zhang; Shu-Ling, Zhang; Lei, Zhao

来源：Antimicrobial Agents and Chemotherapy, 2017, 61(2): AAC.01347-16.

DOI：10.1128/aac.01347-16

<jats:title>ABSTRACT</jats:title>
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This study investigated the antischistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on interleukin 13 (IL-13)/microRNA-21 (miR-21)/Smad7 signaling interactions in the hepatic stellate LX2 cell line and schistosome-infected mice. The transfection was based on the ability of the GV273–miR-21–enhanced green fluorescent protein (EGFP) and GV369–miR-21–EGFP lentiviral system to up- or downregulate the miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7, and connective tissue growth factor (CTGF) and the protein expression of Smad7, CTGF, Smad1, phosphor-Smad1 (p-Smad1), Smad2, p-Smad2, Smad2/3, p-Smad2/3, transforming growth factor β (TGF-β) receptor I, and α-smooth muscle actin (α-SMA) was assayed. Pathological manifestation of hepatic tissue was assessed for the degree of liver fibrosis in animals. The results showed that CGA could inhibit the mRNA expression of miR-21, promote Smad7, and inhibit CTGF mRNA expression. Meanwhile, CGA could significantly lower the protein levels of CTGF, p-Smad1, p-Smad2, p-Smad2/3, TGF-β receptor I, and α-SMA and elevate the Smad7 protein level.
<jats:italic>In vivo</jats:italic>
, with treatment with CGA, the signaling molecules of IL-13/miR-21/Smad7 interactions were markedly regulated. CGA could also reduce the degree of liver fibrosis in pathological manifestations. In conclusion, CGA could inhibit schistosomiasis-induced hepatic fibrosis through IL-13/miR-21/Smad7 signaling interactions in LX2 cells and schistosome-infected mice and might serve as an antifibrosis agent for treating schistosomiasis liver fibrosis.
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• 出版日期2017-2
• 单位华中科技大学