| First Author | Zhang K | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 144 |
| PubMed ID | 28747678 | Mgi Jnum | J:247756 |
| Mgi Id | MGI:5921210 | Doi | 10.1038/s41467-017-00204-4 |
| Citation | Zhang K, et al. (2017) The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFbeta and Notch pathways. Nat Commun 8(1):144 |
| abstractText | Long noncoding RNAs (lncRNAs) play important roles in various biological processes such as proliferation, cell death and differentiation. Here, we show that a liver-enriched lncRNA, named liver fibrosis-associated lncRNA1 (lnc-LFAR1), promotes liver fibrosis. We demonstrate that lnc-LFAR1 silencing impairs hepatic stellate cells (HSCs) activation, reduces TGFbeta-induced hepatocytes apoptosis in vitro and attenuates both CCl4- and bile duct ligation-induced liver fibrosis in mice. Lnc-LFAR1 promotes the binding of Smad2/3 to TGFbetaR1 and its phosphorylation in the cytoplasm. Lnc-LFAR1 binds directly to Smad2/3 and promotes transcription of TGFbeta, Smad2, Smad3, Notch2 and Notch3 which, in turn, results in TGFbeta and Notch pathway activation. We show that the TGFbeta1/Smad2/3/lnc-LFAR1 pathway provides a positive feedback loop to increase Smad2/3 response and a novel link connecting TGFbeta with Notch pathway. Our work identifies a liver-enriched lncRNA that regulates liver fibrogenesis and suggests it as a potential target for fibrosis treatment.Activated hepatic stellate cells are the principal contributors to liver fibrosis by secreting a variety of pro-fibrogenic cytokines . Here Zhang et al. demonstrate that a liver-enriched lncRNA, lnc-LFAR1, promotes liver fibrosis and HSC activation by activating TGFbeta and Notch signaling. |
