{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:04:30Z","timestamp":1791309870126,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T00:00:00Z","timestamp":1379376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"Background and Purpose<\/jats:title>Hepatic fibrosis is a type of liver disease characterized by excessive collagen deposition produced by activated hepatic stellate cells (HSCs<\/jats:styled-content>), and no appropriate drug treatment is available clinically. The microRNA, miR<\/jats:styled-content>\u201021 exhibits an important role in the pathogenesis and progression of hepatic fibrosis. 3,3\u2032\u2010Diindolylmethane (DIM<\/jats:styled-content>) is a natural autolytic product in plants and can down\u2010regulate miR<\/jats:styled-content>\u201021 expression. Here we have assessed the therapeutic effects of DIM<\/jats:styled-content> against hepatic fibrosis and investigated the underlying mechanisms.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>The effects of DIM<\/jats:styled-content> on HSC<\/jats:styled-content> activation were measured by analysing the expression of \u03b1\u2010smooth muscle actin and collagen I<\/jats:styled-content> in both HSC<\/jats:styled-content>\u2010T6 cell line and primary HSCs<\/jats:styled-content>. Expression of miR<\/jats:styled-content>\u201021 was also measured after DIM<\/jats:styled-content> treatment and the therapeutic effect of DIM<\/jats:styled-content> was further studied in vivo<\/jats:italic>, using the model of hepatic fibrosis induced by thioacetamide in mice. The antagonist oligonucleotide, antagomir\u201021, was also used to suppress the effects of miR<\/jats:styled-content>\u201021.<\/jats:p><\/jats:sec>Key Results<\/jats:title>DIM<\/jats:styled-content> suppressed the central TGF<\/jats:styled-content>\u2010\u03b2 signalling pathway underlying HSC<\/jats:styled-content> activation by down\u2010regulating the expression of miR<\/jats:styled-content>\u201021. The decreased miR<\/jats:styled-content>\u201021 expression was achieved by inhibiting the activity of the transcription factor, AP\u20101<\/jats:styled-content>. Moreover, DIM<\/jats:styled-content> blunted the activation phenotype of primary HSCs<\/jats:styled-content>. Administration of DIM<\/jats:styled-content>\u2005in vivo<\/jats:italic> attenuated liver fibrosis induced by thioacetamide, as assessed by collagen deposition and profiles of profibrogenic markers.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>DIM<\/jats:styled-content> shows potential as a therapeutic agent for the treatment of hepatic fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12323","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T14:25:32Z","timestamp":1376490332000},"page":"649-660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["3,3\u2032\u2010Diindolylmethane ameliorates experimental hepatic fibrosis via inhibiting miR<\/scp>\u201021 expression"],"prefix":"10.1111","volume":"170","author":[{"given":"Zhengping","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life 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