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3,3′-Diindolylmethane ameliorates experimental hepatic fibrosis via inhibiting miR-21 expression
Zhang Z.2; Gao Z.2; Hu W.2; Yin S.2; Wang C.3; Zang Y.2; Chen J.2; Zhang J.2; Dong L.2
2013-10-01
Source PublicationBritish Journal of Pharmacology
ISSN00071188 14765381
Volume170Issue:3Pages:649-660
Abstract

Background and Purpose Hepatic fibrosis is a type of liver disease characterized by excessive collagen deposition produced by activated hepatic stellate cells (HSCs), and no appropriate drug treatment is available clinically. The microRNA, miR-21 exhibits an important role in the pathogenesis and progression of hepatic fibrosis. 3,3′-Diindolylmethane (DIM) is a natural autolytic product in plants and can down-regulate miR-21 expression. Here we have assessed the therapeutic effects of DIM against hepatic fibrosis and investigated the underlying mechanisms. Experimental Approach The effects of DIM on HSC activation were measured by analysing the expression of α-smooth muscle actin and collagen I in both HSC-T6 cell line and primary HSCs. Expression of miR-21 was also measured after DIM treatment and the therapeutic effect of DIM was further studied in vivo, using the model of hepatic fibrosis induced by thioacetamide in mice. The antagonist oligonucleotide, antagomir-21, was also used to suppress the effects of miR-21. Key Results DIM suppressed the central TGF-β signalling pathway underlying HSC activation by down-regulating the expression of miR-21. The decreased miR-21 expression was achieved by inhibiting the activity of the transcription factor, AP-1. Moreover, DIM blunted the activation phenotype of primary HSCs. Administration of DIMâ€...in vivo attenuated liver fibrosis induced by thioacetamide, as assessed by collagen deposition and profiles of profibrogenic markers. Conclusions and Implications DIM shows potential as a therapeutic agent for the treatment of hepatic fibrosis. © 2013 The British Pharmacological Society.

Keyword3,3′-diindolylmethane Ap-1 Hepatic Stellate Cells Liver Fibrosis Mir-21 Smad Tgf-β
DOI10.1111/bph.12323
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000324751600017
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Jiangsu Engineering Research Center for MicroRNA Biology
2.Nanjing University
3.University of Macau
Recommended Citation
GB/T 7714
Zhang Z.,Gao Z.,Hu W.,et al. 3,3′-Diindolylmethane ameliorates experimental hepatic fibrosis via inhibiting miR-21 expression[J]. British Journal of Pharmacology,2013,170(3):649-660.
APA Zhang Z..,Gao Z..,Hu W..,Yin S..,Wang C..,...&Dong L..(2013).3,3′-Diindolylmethane ameliorates experimental hepatic fibrosis via inhibiting miR-21 expression.British Journal of Pharmacology,170(3),649-660.
MLA Zhang Z.,et al."3,3′-Diindolylmethane ameliorates experimental hepatic fibrosis via inhibiting miR-21 expression".British Journal of Pharmacology 170.3(2013):649-660.
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