A lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 axis modulates hepatic stellate cell (HSC) activation

Hepatic fibrosis is the wound healing response upon the liver tissue damage caused by multiple stimuli. Targeting activated hepatic stellate cells (HSCs), the major extracellular matrix (ECM)-producing cells within the damaged liver, has been regarded as one of the main treatments for hepatic fibrosis. In the present study, we performed preliminary bioinformatics analysis attempting to identify possible factors related to hepatic fibrosis and found that lncRNA G protein-coupled receptor 137B (Gpr137b-ps) and C-X-C motif chemokine ligand 14 (CXCL14) showed to be markedly upregulated within carbon tetrachloride (CCl4)-caused hepatic fibrotic mice tissue samples and activated HSCs. CXCL14 The silencing of lncRNA Gpr137b-ps or CXCL14 alone could significantly improve CCl4-induced fibrotic changes in mice liver in vivo and collagen I and III release by HSCs and HSC proliferation in vitro. miR-200a-3p directly targeted lncRNA Gpr137b-ps and CXCL14, respectively. LncRNA Gpr137b-ps relieved miR-200a-3p-induced inhibition on CXCL14 expression via acting as a ceRNA. In HSCs, the effects of lncRNA Gpr137b-ps silencing on collagen I and III release by HSCs and HSC proliferation were significantly reversed by miR-200a-3p inhibition, and the effects of miR-200a-3p inhibition were reversed by CXCL14 silencing. In conclusion, we demonstrated a lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 axis that modulates HSC activation and might exert an effect on the pathogenesis of liver fibrosis. (C) 2020 Published by Elsevier B.V.

Automated summary

The study identified a lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 axis that regulates HSC activation and may have an impact on the pathogenesis of liver fibrosis. The silencing of Gpr137b-ps or CXCL14 alone improved fibrotic changes induced by CCl4 in mice liver tissue and HSCs in vivo and in vitro. MiR-200a-3p directly targeted Gpr137b-ps and CXCL14, indicating their role in mediating hepatic fibrosis.