机构:[1]Technology Transfer Center, Kunming Medical University, Kunming 650500, China[2]Department of Anatomy and Histology, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China[3]Department of Neurology, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, China内科科室外科科室神经内科泌尿外科昆明医科大学附属第一医院[4]Department of Cardiology, The Second Affiliated Hospital, Kunming Medical University, Kunming 650032, China
Microglia contribute to the regulation of neuroinflammation and play an important role in the pathogenesis of brain disorders. Thus, regulation of neuroinflammation triggered by activation of microglia has become a promising therapeutic strategy. Here, we investigated the beneficial effects of Gastrodin in activated microglia and analyzed the underlying molecular mechanisms. Microglia activation was regulated by Gastrodin not only in terms of microglia population size but also production of inflammatory mediators. Gastrodin inhibited the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), cyclin-D1 and Ki67 in lipopolysaccharide (LPS)-stimulated BV-2 or primary microglia. Gastrodin also suppressed the expression of iNOS and Ki67 in activated microglia in three-day-old LPS-injected postnatal rats. In addition, the present results have shown that Gastrodin inhibited LPS-induced phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) at Ser 9 and beta-catenin activity. We further extended our investigation to determine whether Wnt/beta-catenin signaling pathway was involved in the anti-inflammatory and anti-proliferation function of Gastrodin. beta-Catenin antagonist (XAV939) was used to block LPS-mediated upregulation of iNOS, TNF-alpha, cyclin-D1, nitric oxide (NO) and the number of cells in the G2/M + S phase of cell cycle. Moreover, treatment with LiCl, a special Wnt/beta-catenin pathway agonist significantly blocked Gastrodin-mediated down-regulation of iNOS, TNF-alpha, cyclin-D1, NO and the number of cells in the G2/M + S phase of cell cycle in LPS-stimulated BV-2 microglia. Taken together, the present results suggested that Gastrodin mediated anti-inflammatory and anti-proliferation effects in activated microglia by modulating the Wnt/beta-catenin signaling pathway.
基金:
National Science Foundation of ChinaNational Natural Science Foundation of China [31760292, 81760087, 81460210, 81460350, 81360200]; Yunnan Applied Basic Research Project [2017FA035, 2018IA048, 2018FE001(-029), 2017FE467(-008), 2018FE001(-017)]
第一作者机构:[1]Technology Transfer Center, Kunming Medical University, Kunming 650500, China
共同第一作者:
通讯作者:
通讯机构:[*1]Department of Neurology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District,Kunming 650032, Yunnan Province, China[*2]Technology Transfer Center, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue,Chenggong District, Kunming 650500, Yunnan Province, China
推荐引用方式(GB/T 7714):
Yao Yue-yi,Bian Li-gong,Yang Ping,et al.Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt/beta-catenin signaling pathway[J].BRAIN RESEARCH.2019,1717:190-203.doi:10.1016/j.brainres.2019.04.025.
APA:
Yao, Yue-yi,Bian, Li-gong,Yang, Ping,Sui, Yue,Li, Run...&Lu, Di.(2019).Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt/beta-catenin signaling pathway.BRAIN RESEARCH,1717,
MLA:
Yao, Yue-yi,et al."Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt/beta-catenin signaling pathway".BRAIN RESEARCH 1717.(2019):190-203