Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury
Abstract The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cel...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/dc498374391b4fd085493c36b3ed9f0a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:dc498374391b4fd085493c36b3ed9f0a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:dc498374391b4fd085493c36b3ed9f0a2021-12-02T12:32:06ZInhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury10.1038/s41598-017-08052-42045-2322https://doaj.org/article/dc498374391b4fd085493c36b3ed9f0a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08052-4https://doaj.org/toc/2045-2322Abstract The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro. In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis.Zili HeShuang ZouJiayu YinZhengzheng GaoYanlong LiuYanqing WuHuacheng HeYulong ZhouQingqing WangJiawei LiFenzan WuHua-Zi XuXiaofeng JiaJian XiaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Zili He Shuang Zou Jiayu Yin Zhengzheng Gao Yanlong Liu Yanqing Wu Huacheng He Yulong Zhou Qingqing Wang Jiawei Li Fenzan Wu Hua-Zi Xu Xiaofeng Jia Jian Xiao Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury |
| description |
Abstract The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro. In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis. |
| format |
article |
| author |
Zili He Shuang Zou Jiayu Yin Zhengzheng Gao Yanlong Liu Yanqing Wu Huacheng He Yulong Zhou Qingqing Wang Jiawei Li Fenzan Wu Hua-Zi Xu Xiaofeng Jia Jian Xiao |
| author_facet |
Zili He Shuang Zou Jiayu Yin Zhengzheng Gao Yanlong Liu Yanqing Wu Huacheng He Yulong Zhou Qingqing Wang Jiawei Li Fenzan Wu Hua-Zi Xu Xiaofeng Jia Jian Xiao |
| author_sort |
Zili He |
| title |
Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury |
| title_short |
Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury |
| title_full |
Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury |
| title_fullStr |
Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury |
| title_full_unstemmed |
Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury |
| title_sort |
inhibition of endoplasmic reticulum stress preserves the integrity of blood-spinal cord barrier in diabetic rats subjected to spinal cord injury |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/dc498374391b4fd085493c36b3ed9f0a |
| work_keys_str_mv |
AT zilihe inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT shuangzou inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT jiayuyin inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT zhengzhenggao inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT yanlongliu inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT yanqingwu inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT huachenghe inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT yulongzhou inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT qingqingwang inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT jiaweili inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT fenzanwu inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT huazixu inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT xiaofengjia inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury AT jianxiao inhibitionofendoplasmicreticulumstresspreservestheintegrityofbloodspinalcordbarrierindiabeticratssubjectedtospinalcordinjury |
| _version_ |
1718394186424647680 |