Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin

The incidence of degenerative spinal diseases, such as cervical spondylosis and thoracic and lumbar disc herniation, is increasing. These health problems have adversely affected human life and work. Surgical intervention is effective when intervertebral disc degeneration (IDD) causes nerve compressi...

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Autores principales:	Haoran Xu, Kang Wei, Jingyao Tu, Yangmengfan Chen, Yi He, Yifan Ding, Huanhuan Xu, Xinyu Bao, Hui Xie, Huang Fang, Huan Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	intervertebral disc degeneration (IDD) inflammation vascular invasion cystathionine-γ-lyase (CSE) E-selectin (CD62E) Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/eac4465803e44672aa1948b84494b077
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spelling	oai:doaj.org-article:eac4465803e44672aa1948b84494b0772021-11-15T05:13:34ZReducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin2296-634X10.3389/fcell.2021.741046https://doaj.org/article/eac4465803e44672aa1948b84494b0772021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.741046/fullhttps://doaj.org/toc/2296-634XThe incidence of degenerative spinal diseases, such as cervical spondylosis and thoracic and lumbar disc herniation, is increasing. These health problems have adversely affected human life and work. Surgical intervention is effective when intervertebral disc degeneration (IDD) causes nerve compression and/or severely limits daily activity. Early IDD patients generally do not require surgery. However, there is no effective method of impeding IDD progression. Thus, novel approaches to alleviating IDD deterioration are urgently required. Cystathionine-γ-lyase (CSE) and E-selectin (CD62E) are vital factors regulating vascular function and inflammation. However, their effects on IDD and vascular invasion in intervertebral discs (IVDs) are pending further exploration. Here, bioinformatics and human nucleus pulposus (NP) tissues analyses revealed that CSE was significantly downregulated and CD62E was upregulated in the NP tissues of IDD patients. We demonstrated that CSE overexpression, CD62E downregulation, and NF-κB (P65) inhibition mitigate inflammation and recover metabolic function in NP cells. Similarly, CSE attenuated vascular invasion induced by inflammatory irritation. Using a rat IDD model, we showed that CSE improved degeneration, inflammation, and microvascular invasion in NP tissue, whereas CD62E had the opposite effect. Taken together, our results indicated that the CSE/CD62E pathway could effectively improve the inflammatory environment and vascular invasion in IVD. Hence, the findings of this study propose a promising and valuable strategy for the treatment of patients with early IDD as well as postoperative adjuvant therapy in patients with severe IDD.Haoran XuKang WeiJingyao TuYangmengfan ChenYi HeYifan DingHuanhuan XuXinyu BaoHui XieHuang FangHuan WangFrontiers Media S.A.articleintervertebral disc degeneration (IDD)inflammationvascular invasioncystathionine-γ-lyase (CSE)E-selectin (CD62E)Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intervertebral disc degeneration (IDD) inflammation vascular invasion cystathionine-γ-lyase (CSE) E-selectin (CD62E) Biology (General) QH301-705.5
spellingShingle	intervertebral disc degeneration (IDD) inflammation vascular invasion cystathionine-γ-lyase (CSE) E-selectin (CD62E) Biology (General) QH301-705.5 Haoran Xu Kang Wei Jingyao Tu Yangmengfan Chen Yi He Yifan Ding Huanhuan Xu Xinyu Bao Hui Xie Huang Fang Huan Wang Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
description	The incidence of degenerative spinal diseases, such as cervical spondylosis and thoracic and lumbar disc herniation, is increasing. These health problems have adversely affected human life and work. Surgical intervention is effective when intervertebral disc degeneration (IDD) causes nerve compression and/or severely limits daily activity. Early IDD patients generally do not require surgery. However, there is no effective method of impeding IDD progression. Thus, novel approaches to alleviating IDD deterioration are urgently required. Cystathionine-γ-lyase (CSE) and E-selectin (CD62E) are vital factors regulating vascular function and inflammation. However, their effects on IDD and vascular invasion in intervertebral discs (IVDs) are pending further exploration. Here, bioinformatics and human nucleus pulposus (NP) tissues analyses revealed that CSE was significantly downregulated and CD62E was upregulated in the NP tissues of IDD patients. We demonstrated that CSE overexpression, CD62E downregulation, and NF-κB (P65) inhibition mitigate inflammation and recover metabolic function in NP cells. Similarly, CSE attenuated vascular invasion induced by inflammatory irritation. Using a rat IDD model, we showed that CSE improved degeneration, inflammation, and microvascular invasion in NP tissue, whereas CD62E had the opposite effect. Taken together, our results indicated that the CSE/CD62E pathway could effectively improve the inflammatory environment and vascular invasion in IVD. Hence, the findings of this study propose a promising and valuable strategy for the treatment of patients with early IDD as well as postoperative adjuvant therapy in patients with severe IDD.
format	article
author	Haoran Xu Kang Wei Jingyao Tu Yangmengfan Chen Yi He Yifan Ding Huanhuan Xu Xinyu Bao Hui Xie Huang Fang Huan Wang
author_facet	Haoran Xu Kang Wei Jingyao Tu Yangmengfan Chen Yi He Yifan Ding Huanhuan Xu Xinyu Bao Hui Xie Huang Fang Huan Wang
author_sort	Haoran Xu
title	Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_short	Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_full	Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_fullStr	Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_full_unstemmed	Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_sort	reducing inflammation and vascular invasion in intervertebral disc degeneration via cystathionine-γ-lyase inhibitory effect on e-selectin
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/eac4465803e44672aa1948b84494b077
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Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin

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