دورية أكاديمية
M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression
| العنوان: | M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression |
|---|---|
| المؤلفون: | En Liang, Shaorong Xiao, Changtong Zhao, Yu Zhang, Guanglei Fu |
| المصدر: | Heliyon, Vol 9, Iss 6, Pp e16905- (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Science (General) LCC:Social sciences (General) |
| مصطلحات موضوعية: | Cerebral ischemia-reperfusion injury, N6-methyladenosine, Blood-brain barrier, Matrix metalloproteinase 3, Oxygen-glucose deprivation and reoxygenation, Science (General), Q1-390, Social sciences (General), H1-99 |
| الوصف: | Blood-brain barrier (BBB) breakdown is a critical event in cerebral ischemia-reperfusion (I/R) injury, and matrix metalloproteinases (MMPs), which are proteolytic enzymes, play essential roles in BBB breakdown through degrading the extracellular matrix. N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has an important role in the progression of cerebral I/R injury. However, whether m6A is related to BBB breakdown and MMPs expression in cerebral I/R injury is still not clear. In this study, we explored the potential effects of m6A modification on BBB breakdown in cerebral I/R injury and its underlying mechanisms using mice subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R), and mouse brain endothelial cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R). We find that MMP3 expression is highly expressed and positively associated with the m6A writer CBLL1 (Cbl proto-oncogene like 1) in cerebral I/R injury in vivo and in vitro. Furthermore, MMP3 mRNA occurs m6A modification in mouse brain endothelial cells, and the m6A modification level of MMP3 mRNA is significantly increased in cerebral I/R injury. Moreover, inhibition of m6A modification reduces MMP3 expression and ameliorates BBB breakdown in cerebral I/R in vivo and in vitro. In conclusion, m6A modification promotes BBB breakdown in cerebral I/R injury through increasing MMP3 expression, indicating that m6A may be a potential therapeutic target for cerebral I/R injury. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-8440 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2405844023041129; https://doaj.org/toc/2405-8440 |
| DOI: | 10.1016/j.heliyon.2023.e16905 |
| URL الوصول: | https://doaj.org/article/44c1926289444198a362ed900916628b |
| رقم الأكسشن: | edsdoj.44c1926289444198a362ed900916628b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24058440 |
|---|---|
| DOI: | 10.1016/j.heliyon.2023.e16905 |