Small Interfering RNA Targeting DMP1 Protects Mice Against Blood-Brain Barrier Disruption and Brain Injury After Intracerebral Hemorrhage
| Autor: | Juan Huang, Shiye Xu, Meng Gao, Shujuan Zhu, Zhengyu Yang, Yuhui Liao, Wei-Tian Lu, Yue Shu, Shengwei Gan |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Small interfering RNA Odontoblast differentiation Brain Edema Pharmacology Occludin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine stomatognathic system Western blot Downregulation and upregulation medicine Animals cardiovascular diseases RNA Small Interfering Cerebral Hemorrhage Evans Blue Intracerebral hemorrhage Extracellular Matrix Proteins medicine.diagnostic_test business.industry Rehabilitation medicine.disease DMP1 nervous system diseases Disease Models Animal Matrix Metalloproteinase 9 chemistry Blood-Brain Barrier Zonula Occludens-1 Protein RNA Interference Surgery Neurology (clinical) Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Stroke and Cerebrovascular Diseases. 30:105760 |
| ISSN: | 1052-3057 |
| DOI: | 10.1016/j.jstrokecerebrovasdis.2021.105760 |
| Popis: | Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment. |
| Databáze: | OpenAIRE |
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