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Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis

Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and inve...

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Autores principales: Zhang, Xiao-Bo, Xu, Si-Qi, Hui, Yi-Geng, Zhou, Hai-Yu, Hu, Yi-Cun, Zhang, Rui-Hao, Gao, Xi-Dan, Zheng, Chang-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186764/
https://www.ncbi.nlm.nih.gov/pubmed/35613904
http://dx.doi.org/10.18632/aging.204100
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author Zhang, Xiao-Bo
Xu, Si-Qi
Hui, Yi-Geng
Zhou, Hai-Yu
Hu, Yi-Cun
Zhang, Rui-Hao
Gao, Xi-Dan
Zheng, Chang-Ming
author_facet Zhang, Xiao-Bo
Xu, Si-Qi
Hui, Yi-Geng
Zhou, Hai-Yu
Hu, Yi-Cun
Zhang, Rui-Hao
Gao, Xi-Dan
Zheng, Chang-Ming
author_sort Zhang, Xiao-Bo
collection PubMed
description Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. Methods: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein–protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1β was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT–PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. Results: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. Conclusion: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.
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spelling pubmed-91867642022-06-14 Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis Zhang, Xiao-Bo Xu, Si-Qi Hui, Yi-Geng Zhou, Hai-Yu Hu, Yi-Cun Zhang, Rui-Hao Gao, Xi-Dan Zheng, Chang-Ming Aging (Albany NY) Research Paper Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. Methods: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein–protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1β was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT–PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. Results: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. Conclusion: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target. Impact Journals 2022-05-25 /pmc/articles/PMC9186764/ /pubmed/35613904 http://dx.doi.org/10.18632/aging.204100 Text en Copyright: © 2022 Zhang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Xiao-Bo
Xu, Si-Qi
Hui, Yi-Geng
Zhou, Hai-Yu
Hu, Yi-Cun
Zhang, Rui-Hao
Gao, Xi-Dan
Zheng, Chang-Ming
Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis
title Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis
title_full Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis
title_fullStr Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis
title_full_unstemmed Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis
title_short Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis
title_sort lactotransferrin promotes intervertebral disc degeneration by regulating fas and inhibiting human nucleus pulposus cell apoptosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186764/
https://www.ncbi.nlm.nih.gov/pubmed/35613904
http://dx.doi.org/10.18632/aging.204100
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