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.

中文翻译：

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lncRNA Gpr137b-ps/miR-200a-3p/CXCL14轴调节肝星状细胞（HSC）活化

肝纤维化是多种刺激引起的肝组织损伤后的伤口愈合反应。靶向活化肝星状细胞 (HSC)，受损肝脏内的主要细胞外基质 (ECM) 生成细胞，已被视为肝纤维化的主要治疗方法之一。在本研究中，我们进行了初步生物信息学分析，试图确定与肝纤维化相关的可能因素，发现 lncRNA G 蛋白偶联受体 137B (Gpr137b-ps) 和 CXC 基序趋化因子配体 14 (CXCL14) 在碳内显着上调四氯化物 (CCl4) 引起的肝纤维化小鼠组织样本和活化的 HSC。CXCL14 单独沉默 lncRNA Gpr137b-ps 或 CXCL14 可以显着改善 CCl4 诱导的体内小鼠肝脏纤维化变化以及 HSC 和体外 HSC 增殖的胶原 I 和 III 释放。miR-200a-3p 分别直接靶向 lncRNA Gpr137b-ps 和 CXCL14。LncRNA Gpr137b-ps 通过充当 ceRNA 解除了 miR-200a-3p 诱导的对 CXCL14 表达的抑制。在HSCs中，lncRNA Gpr137b-ps沉默对HSCs释放I和III胶原以及HSC增殖的影响被miR-200a-3p抑制显着逆转，而miR-200a-3p抑制的作用被CXCL14沉默逆转。总之，我们证明了 lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 轴可调节 HSC 活化并可能对肝纤维化的发病机制产生影响。miR-200a-3p 分别直接靶向 lncRNA Gpr137b-ps 和 CXCL14。LncRNA Gpr137b-ps 通过充当 ceRNA 解除了 miR-200a-3p 诱导的对 CXCL14 表达的抑制。在HSCs中，lncRNA Gpr137b-ps沉默对HSCs释放I和III胶原以及HSC增殖的影响被miR-200a-3p抑制显着逆转，而miR-200a-3p抑制的作用被CXCL14沉默逆转。总之，我们证明了 lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 轴可调节 HSC 活化并可能对肝纤维化的发病机制产生影响。miR-200a-3p 分别直接靶向 lncRNA Gpr137b-ps 和 CXCL14。LncRNA Gpr137b-ps 通过充当 ceRNA 解除了 miR-200a-3p 诱导的对 CXCL14 表达的抑制。在HSCs中，lncRNA Gpr137b-ps沉默对HSCs释放I和III胶原以及HSC增殖的影响被miR-200a-3p抑制显着逆转，而miR-200a-3p抑制的作用被CXCL14沉默逆转。总之，我们证明了 lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 轴可调节 HSC 活化并可能对肝纤维化的发病机制产生影响。lncRNA Gpr137b-ps沉默对HSC释放I型和III型胶原以及HSC增殖的影响被miR-200a-3p抑制显着逆转，而miR-200a-3p抑制的作用被CXCL14沉默逆转。总之，我们证明了 lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 轴可调节 HSC 活化并可能对肝纤维化的发病机制产生影响。lncRNA Gpr137b-ps沉默对HSC释放I型和III型胶原以及HSC增殖的影响被miR-200a-3p抑制显着逆转，而miR-200a-3p抑制的作用被CXCL14沉默逆转。总之，我们证明了 lncRNA Gpr137b-ps/miR-200a-3p/CXCL14 轴可调节 HSC 活化并可能对肝纤维化的发病机制产生影响。