LncRNA Airn maintains LSEC differentiation to alleviate liver fibrosis via the KLF2-eNOS-sGC pathway

• DOI: 10.1186/s12916-022-02523-w
• Publication Date: 2022-09-29T00:02:28Z
• Authors: Ting Chen; Zhemin Shi; Yanmian Zhao; Xiaoxiang Meng; Sicong Zhao; Lina Zheng; Xiaohui Han; Zhimei Hu; Qingbin Yao; Huajiang Lin; Xiaoxiao Du; Kun Zhang; Tao Han; Wei Hong
• Keywords: Hepatic stellate cell; KLF2; Hepatic fibrosis

Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. The dysregulation liver sinusoidal endothelial cell (LSEC) phenotype is critical early event the fibrotic process. However, biological function lncRNAs LSEC still remains unclear.The expression level lncRNA Airn was evaluated both livers and serums, well mouse livers. Gain- loss-of-function experiments were performed to detect effect on differentiation hepatic stellate (HSC) activation fibrosis. Furthermore, RIP, RNA pull-down-immunoblotting, ChIP explore underlying mechanisms Airn.We identified significantly upregulated tissues carbon tetrachloride (CCl4)-induced fibrosis model. Moreover, AIRN serums remarkably increased compared with healthy controls. In vivo studies showed that deficiency aggravated CCl4- bile duct ligation (BDL)-induced fibrosis, while over-expression by AAV8 alleviated CCl4-induced we revealed maintained vitro. Additionally, inhibited HSC indirectly regulating promoted hepatocyte (HC) proliferation increasing paracrine secretion Wnt2a HGF from LSEC. Mechanistically, interacted EZH2 maintain through KLF2-eNOS-sGC pathway, thereby maintaining quiescence promoting HC proliferation.Our work beneficial might be serum biomarker for fibrogenesis.