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However, the regulation of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 receptor I (T\u03b2RI) production by miRNA remains poorly understood. Here we demonstrate that the miR\u2010101 family members act as suppressors of TGF\u03b2 signalling by targeting T\u03b2RI and its transcriptional activator Kruppel\u2010like factor 6 (KLF6) during liver fibrogenesis. Using a mouse model of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced liver fibrosis, we conducted a time\u2010course experiment and observed significant down\u2010regulation of miR\u2010101 in the fibrotic liver as well as in the activated HSCs and injured hepatocytes in the process of liver fibrosis. Meanwhile, up\u2010regulation of T\u03b2RI\/KLF6 was observed in the fibrotic liver. Subsequent investigations validated that T\u03b2RI and KLF6 were direct targets of miR\u2010101. Lentivirus\u2010mediated ectopic expression of miR\u2010101 in liver greatly reduced CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis, whereas intravenous administration of antisense miR\u2010101 oligonucleotides aggravated hepatic fibrogenesis. Mechanistic studies revealed that miR\u2010101 inhibited profibrogenic TGF\u03b2 signalling by suppressing T\u03b2RI expression in both HSCs and hepatocytes. Additionally, miR\u2010101 promoted the reversal of activated HSCs to a quiescent state, as indicated by suppression of proliferation and migration, loss of activation markers and gain of quiescent HSC\u2010specific markers. In hepatocytes, miR\u2010101 attenuated profibrogenic TGF\u03b2 signalling and suppressed the consequent up\u2010regulation of profibrogenic cytokines, as well as TGF\u03b2\u2010induced hepatocyte apoptosis and the inhibition of cell proliferation. The pleiotropic roles of miR\u2010101 in hepatic fibrogenesis suggest that it could be a potential therapeutic target for liver fibrosis. Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. 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