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Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway

BACKGROUND: Renal fibrosis occurs in the end-stage of all chronic kidney disease. Transforming growth factor-β1 (TGF-β1) is a central contributor in fibrosis. Identifying effective biomarkers that targets TGF-β1 is necessary for the development of therapeutic agents for kidney disease. In this study...

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Autores principales: Sun, Han, Ke, Cong, Zhang, Lin, Tian, Changjun, Zhang, Zhihui, Wu, Shuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265746/
https://www.ncbi.nlm.nih.gov/pubmed/32447340
http://dx.doi.org/10.12659/MSM.922029
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author Sun, Han
Ke, Cong
Zhang, Lin
Tian, Changjun
Zhang, Zhihui
Wu, Shuhua
author_facet Sun, Han
Ke, Cong
Zhang, Lin
Tian, Changjun
Zhang, Zhihui
Wu, Shuhua
author_sort Sun, Han
collection PubMed
description BACKGROUND: Renal fibrosis occurs in the end-stage of all chronic kidney disease. Transforming growth factor-β1 (TGF-β1) is a central contributor in fibrosis. Identifying effective biomarkers that targets TGF-β1 is necessary for the development of therapeutic agents for kidney disease. In this study, we investigated the effects and mechanism of long non-coding RNA (LncRNA)-ATB in TGF-β1 induced human kidney 2 (HK-2) cells. MATERIAL/METHODS: We investigated the effects of either overexpression or knockdown of LncRNA-ATB on inflammation, cell apoptosis, and senescence in TGF-β1 induced HK-2 cells. TGF-β1 induced HK-2 cells served as the cell model. The gene level was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and protein expressions by western blot. Cell Counting Kit-8 (CCK-8) assay was performed for assessment of cell viability. Flow cytometry was applied for detection of cell apoptosis. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by corresponding kits. RESULTS: LncRNA-ATB was highly expressed in TGF-β1 induced HK-2 cells. Inflammation, cell apoptosis, and senescence were enhanced by TGF-β1 and these effects were all reduced by knockdown of LncRNA-ATB. Whereas overexpression of LncRNA-ATB had the opposite effects with knockdown of LncRNA-ATB. The TGFβ/SMAD2/3 signaling pathway was activated by TGF-β1 and this effect was further enhanced by LncRNA-ATB overexpression. Silencing LncRNA-ATB inhibited the TGFβ/SMAD2/3 signaling pathway in TGF-β1 induced cells. The effects of LncRNA-ATB overexpression aforementioned in TGF-β1 induced cells were abolished by blockage of the TGFβ/S0MAD2/3 signaling pathway. CONCLUSIONS: LncRNA-ATB overexpression have promoting effects on inflammation, cell apoptosis and senescence in TGF-β1 induced HK-2 cells via activating the TGFβ/SMAD2/3 signaling pathway. LncRNA-ATB act as a key downstream mediator via activating the TGFβ/SMAD2/3 signaling pathway and silencing LncRNA-ATB might be a new strategy for chronic kidney disease treatment.
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spelling pubmed-72657462020-06-04 Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway Sun, Han Ke, Cong Zhang, Lin Tian, Changjun Zhang, Zhihui Wu, Shuhua Med Sci Monit Lab/In Vitro Research BACKGROUND: Renal fibrosis occurs in the end-stage of all chronic kidney disease. Transforming growth factor-β1 (TGF-β1) is a central contributor in fibrosis. Identifying effective biomarkers that targets TGF-β1 is necessary for the development of therapeutic agents for kidney disease. In this study, we investigated the effects and mechanism of long non-coding RNA (LncRNA)-ATB in TGF-β1 induced human kidney 2 (HK-2) cells. MATERIAL/METHODS: We investigated the effects of either overexpression or knockdown of LncRNA-ATB on inflammation, cell apoptosis, and senescence in TGF-β1 induced HK-2 cells. TGF-β1 induced HK-2 cells served as the cell model. The gene level was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and protein expressions by western blot. Cell Counting Kit-8 (CCK-8) assay was performed for assessment of cell viability. Flow cytometry was applied for detection of cell apoptosis. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by corresponding kits. RESULTS: LncRNA-ATB was highly expressed in TGF-β1 induced HK-2 cells. Inflammation, cell apoptosis, and senescence were enhanced by TGF-β1 and these effects were all reduced by knockdown of LncRNA-ATB. Whereas overexpression of LncRNA-ATB had the opposite effects with knockdown of LncRNA-ATB. The TGFβ/SMAD2/3 signaling pathway was activated by TGF-β1 and this effect was further enhanced by LncRNA-ATB overexpression. Silencing LncRNA-ATB inhibited the TGFβ/SMAD2/3 signaling pathway in TGF-β1 induced cells. The effects of LncRNA-ATB overexpression aforementioned in TGF-β1 induced cells were abolished by blockage of the TGFβ/S0MAD2/3 signaling pathway. CONCLUSIONS: LncRNA-ATB overexpression have promoting effects on inflammation, cell apoptosis and senescence in TGF-β1 induced HK-2 cells via activating the TGFβ/SMAD2/3 signaling pathway. LncRNA-ATB act as a key downstream mediator via activating the TGFβ/SMAD2/3 signaling pathway and silencing LncRNA-ATB might be a new strategy for chronic kidney disease treatment. International Scientific Literature, Inc. 2020-05-24 /pmc/articles/PMC7265746/ /pubmed/32447340 http://dx.doi.org/10.12659/MSM.922029 Text en © Med Sci Monit, 2020 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Sun, Han
Ke, Cong
Zhang, Lin
Tian, Changjun
Zhang, Zhihui
Wu, Shuhua
Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway
title Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway
title_full Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway
title_fullStr Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway
title_full_unstemmed Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway
title_short Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway
title_sort long non-coding rna (lncrna)-atb promotes inflammation, cell apoptosis and senescence in transforming growth factor-β1 (tgf-β1) induced human kidney 2 (hk-2) cells via tgfβ/smad2/3 signaling pathway
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265746/
https://www.ncbi.nlm.nih.gov/pubmed/32447340
http://dx.doi.org/10.12659/MSM.922029
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