A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment
Background A series of biochemical responses, including hypoxia and aseptic inflammation, occur in periodontal ligament cells (PDLCs) during periodontal tissue remodeling of orthodontic tooth movement (OTM). However, the role of long non-coding RNA (lncRNA) in these responses is still largely unknown. We investigated the role of the lncRNA SNHG8 in hypoxic and inflammatory responses during OTM and explored the underlying mechanisms. Methods The expression pattern of SNHG8, and hypoxic and inflammatory responses under compressive force were analyzed by qRT-PCR, immunohistochemistry, and western blotting, in vivo and in vitro. The effect of overexpression or knockdown of SNHG8 on the nuclear factor-kappaB (NF-kappa B) pathway was evaluated. RNA sequencing was performed for mechanistic analysis. The interaction between SNHG8 and hypoxia-inducible factor (HIF)-1 alpha was studied using catRAPID, RNA immunoprecipitation, and RNA pulldown assays. The effect of the SNHG8-HIF-1 alpha interaction on the NF-kappa B pathway was determined by western blotting. Results The NF-kappa B pathway was activated, and HIF-1 alpha release was stabilized, in PDLCs under compressive force as well as in OTM model rats. The SNHG8 level markedly decreased both in vivo and in vitro. Overexpression of SNHG8 decreased the expression levels of inflammatory cytokines, the phosphorylation of p65, and the degradation of I kappa B alpha in PDLCs, whereas knockdown of SNHG8 reversed these effects. Mechanically, RNA sequencing showed that differentially expressed genes were enriched in cellular response to hypoxia after SNHG8 overexpression. SNHG8 binds to HIF-1 alpha, thus preventing HIF-1 from activating downstream genes, including those related to the NF-kappa B pathway. Conclusion SNHG8 binds to HIF-1 alpha. During OTM, the expression of SNHG8 dramatically decreased, releasing free functional HIF-1 alpha and activating the downstream NF-kappa B pathway. These data suggest a novel lncRNA-regulated mechanism during periodontal tissue remodeling in OTM.
基金：
National Natural Science Foundation of China [82071119, 82071142]
语种：
外文
WOS：
中科院(CAS)分区：
出版当年[2021]版：
大类|2 区医学
小类|2 区细胞与组织工程2 区细胞生物学2 区医学：研究与实验
最新[2025]版：
大类|2 区医学
小类|2 区细胞与组织工程2 区细胞生物学2 区医学：研究与实验
JCR分区：
出版当年[2020]版：
Q1CELL & TISSUE ENGINEERINGQ1CELL BIOLOGYQ1MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1CELL & TISSUE ENGINEERINGQ1CELL BIOLOGYQ1MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]Peking Univ Sch & Hosp Stomatol, Dept Orthodont, 22 Zhongguancun Ave South, Beijing 100081, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Chenxin,Yang Qiaolin,Han Yineng,et al.A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment[J].STEM CELL RESEARCH & THERAPY.2022,13(1):doi:10.1186/s13287-022-02897-x.
APA：
Wang, Chenxin,Yang, Qiaolin,Han, Yineng,Liu, Hao,Wang, Yue...&Li, Weiran.(2022).A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment.STEM CELL RESEARCH & THERAPY,13,(1)
MLA：
Wang, Chenxin,et al."A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment".STEM CELL RESEARCH & THERAPY 13..1(2022)
医学