Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China.
Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China.
Life Sci. 2019 Oct 15;235:116829. doi: 10.1016/j.lfs.2019.116829. Epub 2019 Sep 1.
Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the specific mechanism of the disease remains unknown, and effective treatments are still lacking. It was reported that Nuclear enriched abundant transcript 1 (NEAT1) obviously was up-regulated in NAFLD model. But the role and underlying mechanism of NEAT1 in NAFLD is unclear.
HepG2 cells were treated by free fatty acids (FFA) and C57BL/6J mice were treated by high-fat diet to establish NAFLD in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of NEAT1, ROCK1, and miR-146a-5p. Western blotting and qRT-PCR were used for measuring expression of protein and mRNA level, respectively. Dual luciferase assay was used to detect the target relationship. Oil Red O staining was used to measure the lipid accumulation. HE staining was used for observing pathological feature of liver tissues.
High levels of NEAT1 and ROCK1, and low level of miR-146a-5p were identified in NAFLD models. NEAT1 could target miR-146a-5p to promote ROCK1 expression. Knockdown of NEAT1, overexpression of miR-146a-5p and knockdown of ROCK1 inhibited lipid accumulation through activating AMPK pathway.
NEAT1 may regulate NAFLD through miR-146a-5p targeting ROCK1, and further affect AMPK/SREBP pathway. This study may provide a new thought for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种严重的肝脏疾病，影响着全球人民的健康。然而，该病的确切机制尚不清楚，有效的治疗方法仍然缺乏。有报道称，核富集丰富转录本 1（NEAT1）在 NAFLD 模型中明显上调。但是，NEAT1 在 NAFLD 中的作用和潜在机制尚不清楚。
用游离脂肪酸（FFA）处理 HepG2 细胞，用高脂肪饮食处理 C57BL/6J 小鼠，分别建立体外和体内 NAFLD 模型。应用细胞转染调节 NEAT1、ROCK1 和 miR-146a-5p 的表达。Western blot 和 qRT-PCR 分别用于测量蛋白和 mRNA 水平的表达。双荧光素酶报告基因检测用于检测靶标关系。油红 O 染色用于测量脂质积累。HE 染色用于观察肝组织的病理特征。
在 NAFLD 模型中发现 NEAT1 和 ROCK1 水平升高，miR-146a-5p 水平降低。NEAT1 可以通过靶向 miR-146a-5p 来促进 ROCK1 的表达。敲低 NEAT1、过表达 miR-146a-5p 和敲低 ROCK1 通过激活 AMPK 通路抑制脂质积累。
NEAT1 可能通过 miR-146a-5p 靶向 ROCK1 调节 NAFLD，并进一步影响 AMPK/SREBP 通路。这项研究为 NAFLD 的治疗提供了新的思路。
