Ye Junfeng, Lin Yuanqiang, Yu Ying, Sun Di
Department of Hepato-Biliary-Pancreatic Surgery, First Hospital, Jilin University, Changchun, 130021, Jilin, People's Republic of China.
Department of Ultrasonography, China-Japan Union Hospital, Jilin University, Changchun , 130021, Jilin, People's Republic of China.
J Transl Med. 2020 Nov 24;18(1):445. doi: 10.1186/s12967-020-02577-5.
Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to play an essential role in non-alcoholic fatty liver disease. However, the role of NEAT1 in regulation of alcoholic steatohepatitis (ASH) remains largely unknown. This study aims to explore the role of NEAT1 in ASH by mediating microRNA-129-5p (miR-129-5p) targeting suppressor of cytokine signaling 2 (SOCS2).
NEAT1, miR-129-5p and SOCS2 expression in serum of ASH patients were assessed. In the in vitro cellular experiment, we transfected siRNAs, oligonucleotides or plasmids into ethanol-induced AML-12 mouse hepatocytes to alter NEAT1 and miR-129-5p expression, and inflammatory factors and lipid content were determined. In the in vivo animal experiment, we injected lentiviruses carrying siRNAs, oligonucleotides or plasmids onto ASH mice (ASH induced by feeding mice a Lieber-DeCarli ethanol diet) to alter NEAT1 and miR-129-5p expression through the tail vein. Serum liver function, blood lipids and inflammatory factors were detected; liver histopathology, liver cell apoptosis, and fibrosis were observed. The relationship between NEAT1 and miR-129-5p, or between miR-129-5p and SOCS2 was verified.
MiR-129-5p was reduced while NEAT1 and SOCS2 were elevated in ASH. Inhibited NEAT1 or elevated miR-129-5p suppressed the elevated lipid metabolism and restrained inflammation reaction in ethanol-stimulated AML-12 cells. The promoted miR-129-5p and inhibited NEAT1 could improve the liver function and repress blood lipid, inflammation reaction, hepatocyte apoptosis and liver fibrosis in ethanol-induced ASH mice. Furthermore, NEAT1 could negatively regulate miR-129-5p to target SOCS2.
We have found that the inhibited NEAT1 could suppress liver fibrosis in ASH mice by promoting miR-129-5p and restraining SOCS2, thereby decelerating the development of ASH.
长链非编码RNA核副斑点组装转录本1（NEAT1）已被报道在非酒精性脂肪性肝病中起重要作用。然而，NEAT1在酒精性脂肪性肝炎（ASH）调控中的作用仍 largely 未知。本研究旨在通过介导微小RNA-129-5p（miR-129-5p）靶向细胞因子信号传导抑制因子2（SOCS2）来探索NEAT1在ASH中的作用。
评估ASH患者血清中NEAT1、miR-129-5p和SOCS2的表达。在体外细胞实验中，我们将小干扰RNA、寡核苷酸或质粒转染到乙醇诱导的AML-12小鼠肝细胞中以改变NEAT1和miR-129-5p的表达，并测定炎症因子和脂质含量。在体内动物实验中，我们通过尾静脉向ASH小鼠（通过给小鼠喂食Lieber-DeCarli乙醇饮食诱导的ASH）注射携带小干扰RNA、寡核苷酸或质粒的慢病毒以改变NEAT1和miR-129-5p的表达。检测血清肝功能、血脂和炎症因子；观察肝脏组织病理学、肝细胞凋亡和纤维化情况。验证NEAT1与miR-129-5p之间，或miR-129-5p与SOCS2之间的关系。
在ASH中，miR-129-5p降低而NEAT1和SOCS2升高。抑制NEAT1或升高miR-129-5p可抑制乙醇刺激的AML-12细胞中脂质代谢的升高并抑制炎症反应。促进miR-129-并抑制NEAT1可改善乙醇诱导的ASH小鼠的肝功能并抑制血脂、炎症反应、肝细胞凋亡和肝纤维化。此外，NEAT1可负向调节miR-129-5p以靶向SOCS2。
我们发现抑制NEAT1可通过促进miR-129-5p并抑制SOCS2来抑制ASH小鼠的肝纤维化，从而减缓ASH的发展。
