Nature communications, 2017-07, Vol.8 (1), p.144-16, Article 144
2017
Details
- Autor(en) / Beteiligte
- Titel
- The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFβ and Notch pathways
- Ist Teil von
- Nature communications, 2017-07, Vol.8 (1), p.144-16, Article 144
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 TGFβ-induced hepatocytes apoptosis in vitro and attenuates both CCl - and bile duct ligation-induced liver fibrosis in mice. Lnc-LFAR1 promotes the binding of Smad2/3 to TGFβR1 and its phosphorylation in the cytoplasm. Lnc-LFAR1 binds directly to Smad2/3 and promotes transcription of TGFβ, Smad2, Smad3, Notch2 and Notch3 which, in turn, results in TGFβ and Notch pathway activation. We show that the TGFβ1/Smad2/3/lnc-LFAR1 pathway provides a positive feedback loop to increase Smad2/3 response and a novel link connecting TGFβ 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 TGFβ and Notch signaling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-017-00204-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_b66f68f91b7c4a3abba46dae2622e5e1
- Format
- –
- Schlagworte
- Animals, Apoptosis - genetics, Bile, Cell Line, Cells, Cultured, Cytokines, Fibrosis, Gene Expression Profiling - methods, HEK293 Cells, Hepatic Stellate Cells - metabolism, Hepatocytes - metabolism, Humans, Liver, Liver - metabolism, Liver Cirrhosis - genetics, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Notch protein, Pathways, Receptors, Notch - genetics, Receptors, Notch - metabolism, RNA, Long Noncoding - genetics, Signal Transduction - genetics, Smad2 Protein - genetics, Smad2 Protein - metabolism, Smad3 Protein - genetics, Smad3 Protein - metabolism, Stellate cells, Transforming Growth Factor beta1 - genetics, Transforming Growth Factor beta1 - metabolism