Department of Neurosurgery, The First People's Hospital of Xiaoshan District of Hangzhou City, 199 Shixin South Road, Xiaoshan District, Hangzhou, 311200, China.
Inflammation. 2019 Oct;42(5):1693-1704. doi: 10.1007/s10753-019-01029-7.
To improve clinical outcomes for patients with traumatic brain injury (TBI), it is necessary to explore the mechanism of traumatic brain injury (TBI)-induced neuroinflammation. Connective tissue growth factors (CTGF) have been reported to be involved in the process of inflammatory response or tissue repair, whereas whether and how CTGF participates in the astrocyte-mediated inflammation after TBI remains unclear. In the present study, the TBI-induced activation of astrocytes and augmentation of inflammatory response were simulated by stimulating rat astrocytes with TGF-β1 or CTGF in cultured conditions. TGF-β1 and CTGF both upregulated the expression of GFAP in astrocytes and facilitated the production of inflammatory cytokines and chemokines. Activation of astrocytes by CTGF is in an autocrine manner. According to the results of Boyden chamber assay, CTGF enhanced the recruitment of peripheral blood mononuclear cells (PBMCs) by reactive astrocytes. Besides, CTGF-mediated activation of astrocytes and augmentation of inflammatory response can be terminated by the inhibitor of ASK1 or p38 and JNK. Thus, our data suggested that CTGF could activate astrocytes in an autocrine manner and promote astrocyte-mediated inflammatory response by triggering the ASK1-p38/JNK-NF-κB/AP-1 pathways in astrocytes. Collectively, our study provided evidence that astrocyte-secreted CTGF serves as an amplifier of neuroinflammatory and could be a potential target for alleviating TBI-induced inflammation.
为改善创伤性脑损伤（TBI）患者的临床预后，有必要探讨创伤性脑损伤（TBI）引起的神经炎症的机制。结缔组织生长因子（CTGF）已被报道参与炎症反应或组织修复过程，但 CTGF 是否以及如何参与 TBI 后星形胶质细胞介导的炎症反应尚不清楚。在本研究中，通过在培养条件下用 TGF-β1 或 CTGF 刺激大鼠星形胶质细胞，模拟 TBI 诱导的星形胶质细胞激活和炎症反应增强。TGF-β1 和 CTGF 均上调星形胶质细胞中 GFAP 的表达，并促进炎症细胞因子和趋化因子的产生。CTGF 通过自分泌方式激活星形胶质细胞。根据 Boyden 室测定的结果，CTGF 增强了反应性星形胶质细胞对外周血单核细胞（PBMC）的募集。此外，CTGF 介导的星形胶质细胞激活和炎症反应增强可被 ASK1 或 p38 和 JNK 的抑制剂终止。因此，我们的数据表明 CTGF 可以通过触发星形胶质细胞中的 ASK1-p38/JNK-NF-κB/AP-1 通路以自分泌方式激活星形胶质细胞，并促进星形胶质细胞介导的炎症反应。总之，我们的研究提供了证据表明星形胶质细胞分泌的 CTGF 作为神经炎症的放大器，并可能成为缓解 TBI 诱导的炎症的潜在靶点。
