FGF20 Protected Against BBB Disruption After Traumatic Brain Injury by Upregulating Junction Protein Expression and Inhibiting the Inflammatory Response.
FGF20 Protected Against BBB Disruption After Traumatic Brain Injury by Upregulating Junction Protein Expression and Inhibiting the Inflammatory Response.
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DOI：
10.3389/fphar.2020.590669
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发表时间：
2020
影响因子：
5.6
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Chen J;Wang X;Hu J;Du J;Dordoe C;Zhou Q;Huang W;Guo R;Han F;Guo K;Ye S;Lin L;Li X
创伤性脑损伤（TBI）后发生的血脑屏障（BBB）破坏和脑炎症反应促进了进一步的脑损伤，从而导致TBI的长期并发症。成纤维细胞生长因子20 （FGF20）是一种神经营养因子，在大脑发育和神经元稳态中起重要作用。本研究的目的是通过血脑屏障维持来评估FGF20对脑外伤的保护作用。在本研究中，重组人FGF20 （rhFGF20）减少了TBI小鼠模型的神经功能缺损、脑水肿、埃文斯蓝外渗和神经炎症。在体外TNF-α诱导的脑血脑屏障破坏的人微血管内皮细胞（HBMEC）模型中，rhFGF20降低了细胞旁通透性，增加了跨内皮电阻（TEER）。在TBI小鼠模型和体外实验中，rhFGF20均可增加血脑屏障相关紧密连接（TJs）和粘附连接（AJs）蛋白的表达，降低炎症反应，保护血脑屏障的完整性。值得注意的是，rhFGF20通过激活AKT/GSK3β通路来维持血脑屏障功能，并通过调节JNK/NFκB通路来抑制炎症反应。因此，FGF20是TBI的潜在候选治疗方法，通过上调连接蛋白表达和抑制炎症反应来保护血脑屏障。
Disruption of the blood-brain barrier (BBB) and the cerebral inflammatory response occurring after traumatic brain injury (TBI) facilitate further brain damage, which leads to long-term complications of TBI. Fibroblast growth factor 20 (FGF20), a neurotrophic factor, plays important roles in brain development and neuronal homeostasis. The aim of the current study was to assess the protective effects of FGF20 on TBI via BBB maintenance. In the present study, recombinant human FGF20 (rhFGF20) reduced neurofunctional deficits, brain edema, Evans blue extravasation and neuroinflammation in a TBI mouse model. In an in vitro TNF-α-induced human brain microvascular endothelial cell (HBMEC) model of BBB disruption, rhFGF20 reduced paracellular permeability and increased trans-endothelial electrical resistance (TEER). Both in the TBI mouse model and in vitro, rhFGF20 increased the expression of proteins composing in BBB-associated tight junctions (TJs) and adherens junctions (AJs), and decreased the inflammatory response, which protected the BBB integrity. Notably, rhFGF20 preserved BBB function by activating the AKT/GSK3β pathway and inhibited the inflammatory response by regulating the JNK/NFκB pathway. Thus, FGF20 is a potential candidate treatment for TBI that protects the BBB by upregulating junction protein expression and inhibiting the inflammatory response.
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