Journal
ACTA PHARMACEUTICA SINICA B
Volume 11, Issue 11, Pages 3493-3507Publisher
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2021.03.032
Keywords
Traumatic brain injury; Exosome; MiRNA-21; Blood-brain barrier; Ginsenoside Rg1; Nonmuscle myosin IIA
Categories
Funding
- National Natural Science Foundation of China [81601034, 31850410476]
- Anhui Provincial Science Fund for Distinguished Young Scholars (China) [2008085J39]
- Focus on Research and Development Projects in Anhui Province (China) [1804a0802225]
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, China) [CMEMR2020-B13]
- Natural Science Foundation of Anhui Educational Committee (China) [KJ2018ZD044, KJ2020A0728]
- Key Disciplines of Pharmacy (China) [2019xjzdxk2]
- Back-up Candidates for Academic and Technical Leaders of Suzhou University (China) [2018XJHB06]
- Key Research Project of Suzhou University (China) [2019yzd06]
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During traumatic brain injury, increased expression of circulatory miR-21 can serve as a diagnostic feature. Low levels of exosome-miR-21 in the brain can improve neuroinflammation and BBB permeability, and Rg1 can protect BBB integrity by inhibiting the release of Exos-miR-21.
During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood-brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1 beta-induced macrophages (IIM)-Exos-miR-21 can activate NF-kappa B signaling pathway and induce the expressions of MMP-1,-3 and -9 and dwnregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA-HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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