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 bloodebrain barri...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 bloodebrain 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-1β-induced macrophages(ⅡA)-Exos-miR-21 can activate NF-kB signaling pathway and induce the expressions of MMP-1,-3 and-9 and downregulate the levels of tight junction proteins(TJPs)deteriorating the BBB.Rg1 reduced miR-21-5 p content in ⅡA-Exos(RⅡA-Exos).The interaction of NMIIAe 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.展开更多
基金supported by National Natural Science Foundation of China(81601034 and 31850410476)Anhui Provincial Science Fund for Distinguished Young Scholars(2008085J39,China)+5 种基金Focus on Research and Development Projects in Anhui Province(1804a0802225,China)State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(CMEMR2020B13,Guangxi Normal University,China)the Natural Science Foundation of Anhui Educational Committee(KJ2018ZD044 and KJ2020A0728,China)Key Disciplines of Pharmacy(2019xjzdxk2,China)the Back-up Candidates for Academic and Technical Leaders of Suzhou University(2018XJHB06,China)Key Research Project of Suzhou University(2019yzd06,China)。
文摘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 bloodebrain 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-1β-induced macrophages(ⅡA)-Exos-miR-21 can activate NF-kB signaling pathway and induce the expressions of MMP-1,-3 and-9 and downregulate the levels of tight junction proteins(TJPs)deteriorating the BBB.Rg1 reduced miR-21-5 p content in ⅡA-Exos(RⅡA-Exos).The interaction of NMIIAe 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.
