title: The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals.
abstract: Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. wzlbye@126.com.
authors.forename: Libing
authors.initials: L
authors.lastname: Ye
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. yangyingmmm@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Ningbo Medical Treatment Center, Li Huili Hospital, Ningbo 315040, China. rennie22@126.com.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. caipingtaowzmu@163.com.
authors.forename: Pingtao
authors.initials: P
authors.lastname: Cai
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. xiaoerrui1989@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Emergency Department, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. cdq1965@126.com.
authors.forename: Daqing
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University, Cixi, Ningbo 315300, China. wxj5100@126.com.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, China. binggun123456@163.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. xhzwmu@126.com.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. xfxj2000@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. xiaokunli@163.com.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. linli@wmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. hyzhang@wmu.edu.cn.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology*; D016328:NF-kappa B; D058580:Neurocan / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D014746:Vimentin / Q000235:genetics
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D058580:Neurocan; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014746:Vimentin; D016222:Fibroblast Growth Factor 2
keywords: GFAP; TLR4/NFκB; astrocytes; bFGF; vimentin