Curcumin inhibits glial scar formation by suppressing astrocyte-induced inflammation and fibrosis in vitro and in vivo.
Curcumin inhibits glial scar formation by suppressing astrocyte-induced inflammation and fibrosis in vitro and in vivo.
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姜黄素通过抑制体外和体内星形胶质细胞诱导的炎症和纤维化来抑制神经胶质疤痕形成。
DOI：
10.1016/j.brainres.2016.11.002
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Lin Jiangkai
中科院分区：
文献类型：
--
作者：
Yuan Jichao;Liu Wei;Zhu Haitao;Chen Yaxing;Zhang Xuan;Li Lan;Chu Weihua;Wen Zexian;Feng Hua;Lin Jiangkai
脊髓损伤(SCI)导致星形胶质细胞形成胶质瘢痕，严重阻碍神经再生。姜黄素(Cur)可抑制胶质瘢痕形成，但其机制尚不完全清楚。本研究通过体内和体外实验，研究了Cur和siRNA干预后星形胶质细胞在炎症和纤维化过程中的表型转化，并确定了Cur治疗与胶质瘢痕成分GFAP和CSPG之间关系的细节。我们发现Cur和NF-κb p65siRNA可以通过抑制NF-κb信号通路抑制星形胶质细胞的活化，从而下调星形胶质细胞释放的趋化因子MCP-1、RANTES和CXCL10的表达，减少巨噬细胞和T细胞的浸润，从而减轻胶质瘢痕的炎症反应。此外，沉默SOX-9可减少细胞外基质CSPG的沉积，而其过表达可增加CSPG的表达。Cur可抑制SOX-9诱导的CSPG沉积，减少星形胶质细胞α-SMA(纤维化的重要标志)的表达，改变星形胶质细胞表型，并通过调节纤维化抑制胶质瘢痕的形成。本研究证实，Cur通过对大鼠脊髓损伤后炎症和纤维化的双重靶点调控，同时调节NF-κb和SOX9信号通路，减少细胞内和细胞外胶质瘢痕成分的表达。这项研究提供了一个重要的假设，即细胞内和细胞外胶质瘢痕成分的双重抑制作为脊髓损伤的治疗策略。
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.