基因敲除
上睑下垂
帕金
染色质免疫沉淀
PTEN公司
分子生物学
化学
下调和上调
细胞生物学
张力素
生物
癌症研究
PI3K/AKT/mTOR通路
信号转导
免疫学
炎症
医学
细胞凋亡
炎症体
基因表达
生物化学
病理
基因
疾病
发起人
帕金森病
作者
Jin-Mei Jiang,Mei-Li Mo,Xiaoping Long,Liang Xie
出处
期刊:Autoimmunity
[Informa]
日期:2021-11-03
卷期号:55 (1): 21-31
被引量:12
标识
DOI:10.1080/08916934.2021.1983802
摘要
Rheumatoid arthritis (RA) often leads to functional disabilities and deformities. MiRNA plays a vital role in cell pyroptosis. Nevertheless, the function and underlying mechanism of miR-144-3p in pyroptosis during the progression of RA remains unclear. In this study, N1511 cells were stimulated with IL-1β to construct a RA model. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess the cell viability. Cell pyroptosis was detected by flow cytometry. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-18) were assessed by enzyme-linked immunosorbent assay (ELISA). The relationship among specific protein 1 (SP1), microRNA-144-3p (miR-144-3p), and phosphatase and tensin homolog (PTEN) was explored by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP), respectively. The level of miR-144-3p in N1511 cells was upregulated by IL-1β. MiR-144-3p knockdown inhibited IL-1β-induced pyroptosis in N1511 cells, and the expressions of NOD-like receptor family pyrin domain containing 3 (NLRP3), Cleaved caspase-1, Gasdermin D (GSDMD), and Cleaved caspase-3 in IL-1β-stimulated N1511 cells were increased. The levels of inflammatory cytokines in N1511 cells were increased by IL-1β, which were restored by miR-144-3p knockdown. MiR-144-3p knockdown abolished IL-1β-induced inactivation of putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein (Parkin) signalling. Moreover, transcription factor SP1 could upregulate miR-144-3p expression and miR-144-3p negatively regulated PTEN expression. In summary, MiR-144-3p induced by SP1 could promote IL-1β-induced chondrocyte pyroptosis via inhibiting PTEN expression and suppressing the activation of PINK1/Parkin signalling, which provided a new strategy against RA.
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