MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke
Although recanalization via thrombolysis and/or thrombectomy has proven to be a beneficial treatment for ischemic stroke, their application are severely limited due to increased risk of symptomatic intracerebral hemorrhage (ICH) as a result of ongoing blood brain barrier (BBB) damage. Degradation of...
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KeAi Communications Co., Ltd.
2021-06-01
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doaj-e44280db94274712886374e551776fc12021-07-01T04:35:18ZengKeAi Communications Co., Ltd.Brain Hemorrhages2589-238X2021-06-01226370MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic strokeRong Pan0Wenlan Liu1Ke Jian Liu2Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USAThe Central Laboratory, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People’s Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, ChinaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA; Corresponding author at: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.Although recanalization via thrombolysis and/or thrombectomy has proven to be a beneficial treatment for ischemic stroke, their application are severely limited due to increased risk of symptomatic intracerebral hemorrhage (ICH) as a result of ongoing blood brain barrier (BBB) damage. Degradation of tight junction protein is a key feature of BBB disruption, while endothelial cell death is a major factor in compromising BBB and subsequent ICH. We recently reported that ischemia-induced cleavage of occludin led to the production of two major occludin fragments, which were detectable in the blood circulation of ischemic stroke rats. Here, we show that one of the occludin fragment (55-kDa) was generated by the cleavage of matrix metalloproteinase (MMP)-2/9. Moreover, the treatment of endothelial cells with the MMP-cleaved occludin fragment dramatically increased cell death compared with treatment with whole occludin protein, suggesting this 55-kDa occludin fragment as a key factor in inducing endothelial cell death. Our findings demonstrate that MMP-2/9 cleaved occludin fragment may contribute to BBB damage following ischemic stroke through promoting endothelial cell death.http://www.sciencedirect.com/science/article/pii/S2589238X21000036Ischemic strokeOccludin55-kDa occludin fragmentMMP-2/9Endothelial cell death |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rong Pan Wenlan Liu Ke Jian Liu |
spellingShingle |
Rong Pan Wenlan Liu Ke Jian Liu MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke Brain Hemorrhages Ischemic stroke Occludin 55-kDa occludin fragment MMP-2/9 Endothelial cell death |
author_facet |
Rong Pan Wenlan Liu Ke Jian Liu |
author_sort |
Rong Pan |
title |
MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke |
title_short |
MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke |
title_full |
MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke |
title_fullStr |
MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke |
title_full_unstemmed |
MMP-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke |
title_sort |
mmp-2/9-cleaved occludin promotes endothelia cell death in ischemic stroke |
publisher |
KeAi Communications Co., Ltd. |
series |
Brain Hemorrhages |
issn |
2589-238X |
publishDate |
2021-06-01 |
description |
Although recanalization via thrombolysis and/or thrombectomy has proven to be a beneficial treatment for ischemic stroke, their application are severely limited due to increased risk of symptomatic intracerebral hemorrhage (ICH) as a result of ongoing blood brain barrier (BBB) damage. Degradation of tight junction protein is a key feature of BBB disruption, while endothelial cell death is a major factor in compromising BBB and subsequent ICH. We recently reported that ischemia-induced cleavage of occludin led to the production of two major occludin fragments, which were detectable in the blood circulation of ischemic stroke rats. Here, we show that one of the occludin fragment (55-kDa) was generated by the cleavage of matrix metalloproteinase (MMP)-2/9. Moreover, the treatment of endothelial cells with the MMP-cleaved occludin fragment dramatically increased cell death compared with treatment with whole occludin protein, suggesting this 55-kDa occludin fragment as a key factor in inducing endothelial cell death. Our findings demonstrate that MMP-2/9 cleaved occludin fragment may contribute to BBB damage following ischemic stroke through promoting endothelial cell death. |
topic |
Ischemic stroke Occludin 55-kDa occludin fragment MMP-2/9 Endothelial cell death |
url |
http://www.sciencedirect.com/science/article/pii/S2589238X21000036 |
work_keys_str_mv |
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