Synthetic VSMCs induce BBB disruption mediated by MYPT1 in ischemic stroke
| العنوان: | Synthetic VSMCs induce BBB disruption mediated by MYPT1 in ischemic stroke |
|---|---|
| المؤلفون: | Pinyi Liu, Hailan Meng, Min-Sheng Zhu, Lizhen Fan, Xinyu Bao, Jian Chen, Liwen Zhu, Yun Xu, Zhijun Pu, Cun-Jin Zhang |
| المصدر: | iScience, Vol 24, Iss 9, Pp 103047-(2021) iScience |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, Cell biology, Vascular smooth muscle, Contraction (grammar), Science, Immunology, MYOSIN PHOSPHATASE TARGET SUBUNIT 1, Phenotypic switching, Article, Medicine, Molecular physiology, Multidisciplinary, business.industry, Chemistry, musculoskeletal system, Brain infarction, Knockout mouse, Ischemic stroke, cardiovascular system, business, tissues, Bbb permeability, Function (biology) |
| الوصف: | Summary Vascular smooth muscle cells (VSMCs) have been widely recognized as key players in regulating blood-brain barrier (BBB) function, and their roles are unclear in ischemic stroke. Myosin phosphatase target subunit 1 (MYPT1) is essential for VSMC contraction and maintaining healthy vasculature. We generated VSMC-specific MYPT1 knockout (MYPT1SMKO) mice and cultured VSMCs infected with Lv-shMYPT1 to explore phenotypic switching of VSMCs and the accompanied impacts on BBB integrity. We found that MYPT1 deficiency induced phenotypic switching of synthetic VSMCs, which aggravated BBB disruption. Proteomic analysis identified evolutionarily conserved signaling intermediates in Toll pathways (ECSIT) as a downstream molecule that promotes activation of synthetic VSMCs and contributed to IL-6 expression. Knocking down ECSIT rescued phenotypic switching of VSMCs and BBB disruption. Additionally, inhibition of IL-6 decreased BBB permeability. These findings reveal that MYPT1 deficiency activated phenotypic switching of synthetic VSMCs and induced BBB disruption through ECSIT-IL-6 signaling after ischemic stroke. Graphical abstract Highlights • MYPT1 deficiency induces activation of synthetic VSMCs and aggravates BBB disruption • Synthetic VSMCs release more IL-6 to destroy BBB in a contact-independent way • MYPT1-ECSIT-IL-6 signaling pathway regulates synthetic VSMC-mediated BBB disruption Immunology; Molecular physiology; Cell biology; Proteomics |
| تدمد: | 2589-0042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dad1a939728dbd633a7e7327b334c6a1 https://doi.org/10.1016/j.isci.2021.103047 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dad1a939728dbd633a7e7327b334c6a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25890042 |
|---|