Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway

Abstract This study was conducted to explore the roles and related mechanisms of lncRNA-TCONS_00147848 (TCONS_00147848) in nasal mucosa cell apoptosis and allergic rhinitis (AR). AR mice were sensitized with ovalbumin (OVA), with the TCONS_00147848 interference lentiviral vector (TCONS_00147848 shRN...

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Autores principales: Haiyun Huang, Yu Ren, Hongyu Liang, Xiaojia Liu, Jisangmo Nan, Hui Zhao, Xiaoling Liu
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:bd13a23fa79747b3ace798d71057e9a02021-12-02T18:49:36ZMechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway10.1038/s41598-021-94215-32045-2322https://doaj.org/article/bd13a23fa79747b3ace798d71057e9a02021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94215-3https://doaj.org/toc/2045-2322Abstract This study was conducted to explore the roles and related mechanisms of lncRNA-TCONS_00147848 (TCONS_00147848) in nasal mucosa cell apoptosis and allergic rhinitis (AR). AR mice were sensitized with ovalbumin (OVA), with the TCONS_00147848 interference lentiviral vector (TCONS_00147848 shRNA) and FOSL2 overexpressing lentiviral vectors (pCDH-FOSL2) constructed respectively. NC shRNA, TCONS_00147848 shRNA and TCONS_00147848 shRNA + pCDH-FOSL2 were transfected into AR mice and mice with TNF-α induced nasal mucosa cells. The allergic reaction symptoms were evaluated by scoring. And in this study, we used Hematoxylin–Eosin (HE) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to detect the histological changes of nasal mucosa and apoptosis of nasal mucosa epithelial cells in mice, cell counting kit-8 (CCK-8) assay, Transwell and annexin V/PI to detect proliferation, migration and apoptosis of nasal mucosa cells of mice, respectively, enzyme-linked immunosorbent assay (ELISA) to detect the expression of inflammatory factors, qRT-PCR to detect TCONS_00147848 expression, Western blot assay to detect the expressions of FOSL2, JAK-2, STAT3, p-STAT3, BAX and BCL-2, RNA-binding protein immunoprecipitation (RIP) assay, RNA pull down assay and Co-immunoprecipitation (CoIP) assay to identify TCONS_00147848 targeting FOSL2. All these findings above reveal that knocking down TCONS_00147848 can reduce the allergic reaction symptom score of AR mice and the inflammatory reaction. The expression of IgE, IL-4, IL-5, IL-10, IL-9, IFN-γ and TNF-α in serum decreased. The expression of FOSL2, JAK-2, p-STAT3 and BAX in nasal mucosa and nasal mucosa cells of mice decreased as well, but BCL-2 expression increased. In addition, koncking down TCONS_00147848 can also inhibit the apoptosis of TNF-α induced nasal mucosa cells in mice and promote cell proliferation and migration. However, FOSL2 overexpression neutralized the effect of TCONS_00147848 shRNA. In nasal mucosa cells of mice, TCONS_00147848 can target FOSL2, interacting with STAT3. Inhibition of TCONS_00147848 can regulate JAK/STAT3 signaling pathway and reduce inflammatory response in AR mice.Haiyun HuangYu RenHongyu LiangXiaojia LiuJisangmo NanHui ZhaoXiaoling LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Haiyun Huang
Yu Ren
Hongyu Liang
Xiaojia Liu
Jisangmo Nan
Hui Zhao
Xiaoling Liu
Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway
description Abstract This study was conducted to explore the roles and related mechanisms of lncRNA-TCONS_00147848 (TCONS_00147848) in nasal mucosa cell apoptosis and allergic rhinitis (AR). AR mice were sensitized with ovalbumin (OVA), with the TCONS_00147848 interference lentiviral vector (TCONS_00147848 shRNA) and FOSL2 overexpressing lentiviral vectors (pCDH-FOSL2) constructed respectively. NC shRNA, TCONS_00147848 shRNA and TCONS_00147848 shRNA + pCDH-FOSL2 were transfected into AR mice and mice with TNF-α induced nasal mucosa cells. The allergic reaction symptoms were evaluated by scoring. And in this study, we used Hematoxylin–Eosin (HE) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to detect the histological changes of nasal mucosa and apoptosis of nasal mucosa epithelial cells in mice, cell counting kit-8 (CCK-8) assay, Transwell and annexin V/PI to detect proliferation, migration and apoptosis of nasal mucosa cells of mice, respectively, enzyme-linked immunosorbent assay (ELISA) to detect the expression of inflammatory factors, qRT-PCR to detect TCONS_00147848 expression, Western blot assay to detect the expressions of FOSL2, JAK-2, STAT3, p-STAT3, BAX and BCL-2, RNA-binding protein immunoprecipitation (RIP) assay, RNA pull down assay and Co-immunoprecipitation (CoIP) assay to identify TCONS_00147848 targeting FOSL2. All these findings above reveal that knocking down TCONS_00147848 can reduce the allergic reaction symptom score of AR mice and the inflammatory reaction. The expression of IgE, IL-4, IL-5, IL-10, IL-9, IFN-γ and TNF-α in serum decreased. The expression of FOSL2, JAK-2, p-STAT3 and BAX in nasal mucosa and nasal mucosa cells of mice decreased as well, but BCL-2 expression increased. In addition, koncking down TCONS_00147848 can also inhibit the apoptosis of TNF-α induced nasal mucosa cells in mice and promote cell proliferation and migration. However, FOSL2 overexpression neutralized the effect of TCONS_00147848 shRNA. In nasal mucosa cells of mice, TCONS_00147848 can target FOSL2, interacting with STAT3. Inhibition of TCONS_00147848 can regulate JAK/STAT3 signaling pathway and reduce inflammatory response in AR mice.
format article
author Haiyun Huang
Yu Ren
Hongyu Liang
Xiaojia Liu
Jisangmo Nan
Hui Zhao
Xiaoling Liu
author_facet Haiyun Huang
Yu Ren
Hongyu Liang
Xiaojia Liu
Jisangmo Nan
Hui Zhao
Xiaoling Liu
author_sort Haiyun Huang
title Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway
title_short Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway
title_full Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway
title_fullStr Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway
title_full_unstemmed Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway
title_sort mechanism of tcons_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through fosl2-mediated jak/stat3 signaling pathway
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/bd13a23fa79747b3ace798d71057e9a0
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