title: Curcumin inhibits glial scar formation by suppressing astrocyte-induced inflammation and fibrosis in vitro and in vivo.
abstract: Spinal cord injury (SCI) leads to glial scar formation by astrocytes, which severely hinders neural regeneration. Curcumin (cur) can inhibit glial scar formation, but the underlying mechanism is not fully understood. Using both in vivo and in vitro experiments, the current study investigated the phenotypic transformation of astrocytes following cur and siRNA intervention during the processes of inflammation and fibrosis and determined details of the relationship between cur treatment and the glial scar components GFAP and CSPG. We found that cur and NF-κb p65 siRNA could inhibit astrocyte activation through suppressing NF-κb signaling pathway, which led to down-regulate the expression of chemokines MCP-1, RANTES and CXCL10 released by astrocytes and decreased macrophage and T-cell infiltration, thus reducing the inflammation in the glial scar. In addition, silencing SOX-9 may reduce the deposition of extracellular matrix CSPG; whereas its over-expression could increase the CSPG expression. Cur suppressedSOX-9-inducedCSPG deposition, reduced α-SMA (an important symbol of fibrosis) expression in astrocytes, altered astrocyte phenotype, and inhibited glial scar formation by regulating fibrosis. This study confirmed that cur could regulate both the NF-κb and SOX9 signaling pathways and reduce the expression of intracellular and extracellular glial scar components through dual-target regulating both inflammation and fibrosis after SCI in the rat. This study provides an important hypothesis centered on the dual inhibition of intracellular and extracellular glial scar components as a treatment strategy for SCI.
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: 531014699@qq.com.
authors.forename: Jichao
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: woshiliuwei2012@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: woshihaitao2012@sina.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: yaxingchensyd@sina.com.
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: 504993085@qq.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: woshililan2015@sina.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: chuweihua2015@sina.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Chu
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: wenzexiansyd@sina.com.
authors.forename: Zexian
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: 496017714@qq.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China. Electronic address: jklin@tmmu.edu.cn.
authors.forename: Jiangkai
authors.initials: J
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; D051996:Transcription Factor RelA; C498145:Rela protein, rat; C498862:Acta2 protein, rat
keywords: Curcumin; Dual-target therapy; Glial scar; NF-κb; SOX9