Research context and trend of TBK1 in autoimmunity, signaling pathways, gene expression, tumor prevention and treatment

Abstract

Abstract: Abstract
BACKGROUND: To explore the research status, hot spots, and trends of TBK1 based on bibliometric analysis and provide references and suggestions for the further basic research of TBK1.
Method: We collected TBK1 articles for the last 10 years based on the SCIE database in the Web of Science Core Collection. The data were imported into CiteSpace 6.3.R1 and analyzed bibliometrically and visually with five options: Country, Author, Institution, Reference, and Keyword, respectively. In addition, we used Origin 2021 to plot the relevant statistical graphs.
Result: There was an upward trend in the number of publications and co-citations involved in TBK1 research. Dan-Dan Chen, Jian-Fang Gui, Qiwei Qin, and Shun Li were the four authors with the highest number of publications (11), while the Chinese Academy of Sciences, University of Chinese Academy of Sciences, Zhejiang University, Chinese Academy of Agricultural Sciences, and Wuhan University had a larger number of publications (> 50). The research hot spots of TBK1 in the last decade mainly focused on innate immunity, the cGAS-STING pathway, NF-κB, inflammation, optineurin, expression, cancer, etc. Conclusion In recent years, academics from various countries conducted sustained and in-depth research in related fields. TBK1 showed great potential for research in the autoimmune system, signaling pathways, gene expression, tumor control, and so on. But academic cooperation between academics and between institutions was not strong. In the future, cooperation and communication should be strengthened to grasp the research hot spots and trends of TBK1, to expand its research range in disease areas, and to provide more evidence for further elucidating the pharmacodynamic mechanisms and pathological changes of diseases

Key words: TBK1, CiteSpace, Web of Science, bibliometrics, visualization, co-citation, research hotspot, frontier

CLC Number:

Xu Canli, He Wenxing, Wang Yuping, Ba Yinying, Chi Li, Wang Wenjuan, Wang Jiajia. Research context and trend of TBK1 in autoimmunity, signaling pathways, gene expression, tumor prevention and treatment[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(在线): 1-11.

Figures/Tables 15

2.5 TBK1文献共被引分析文献共被引分析是文献计量学的一种独特的计量方法，能够用于研究文献之间和各领域之间的影响力和联系。共被引次数是反映一篇文章影响力的重要指标。值得注意的是由于引用延迟以及Citespace软件只能对Web of Science等有限的几个数据库进行文献共被引分析，而中国知网、万方等数据库的文章不能纳入研究，因此共被引次数只能代表特定数据库和特定时期某篇文章的影响力。尽管如此，文献共被引次数还是可以用于探析研究动态、趋势以及该领域的热点。该文总结了2015-2025年2月在Web of Science上发表的所有关于TBK1文献共被引数据，见图7和表4。其中共被引频数最高的文章是Zhang等[15]于2019年发表在《Nature》上的Structural basis of STING binding with and phosphorylation by TBK1(121次)，突现强度为20.67。他们发现STING的C端尾部呈β链状构象，能够插入TBK1二聚体中一个亚基的激酶结构域与第二个亚基的支架和二聚化结构域之间的沟槽中，但是STING尾部的磷酸化位点Ser366无法到达结合的TBK1的激酶域活性位点。鉴于此，他们成功验证了在环二核苷酸(cyclic GMP-AMP，cGAMP)诱导下STING和TBK1的高阶寡聚化导致STING被TBK1磷酸化的模型。 2015年Liu等[16]发表在《Science》的Phosphorylation of innate immune adaptor proteins MAVS，STING，and TRIF induces IRF3 activation文章共被引频数排名第二(108次)，突现强度高达27.88。研究发现线粒体抗病毒蛋白(MAVS)和STING 含有两个保守的Ser和Thr簇，在受到刺激时会被激酶IKK和/或TBK1磷酸化。磷酸化的MAVS和STING会与干扰素调节因子3(IRF3)带正电荷的表面结合，从而招募IRF3使其磷酸化并被TBK1激活。进一步研究发现，Toll样受体信号转导中的β干扰素TIR结构域衔接蛋白也通过类似的磷酸化依赖机制激活IRF3。共被引频数排名第三的是Freischmidt等[17]发表在《Nature Neuroscience》的Haploinsufficiency of TBK1 causes familial ALS and fronto- temporal dementia(102次)，突现强度为21.27。他们对252例家族性肌萎缩性脊髓侧索硬化症患者和827例对照个体进行了外显子组测序实验，发现单倍体TBK1缺乏会导致肌萎缩性脊髓侧索硬化症和额颞叶痴呆症。 Hopfner等[18]发表在《Nature Reviews Molecular Cell Biology》的Molecular mechanisms and cellular functions of cGAS-STING signalling文章共被引频次排到了第4位(96次)，突现强度为24.42。这篇文章以综述的形式回顾了cGAS-STING激活与信号传导的分子机制和细胞功能。Gui等[19]在《Nature》发表的文章共被引频次达到了85次，排名第5，这篇文章名为Autophagy induction via STING trafficking is a primordial function of the cGAS pathway。作者们报告了STING能通过一种独立于TBK1激活和干扰素诱导的机制激活自噬。STING与cGAMP结合后，会转位到内质网-高尔基体中间区室和高尔基体，这一过程依赖于COP-II复合物和ARF GTP酶。含STING的内质网-高尔基体中间区室是微管相关蛋白1轻链3脂化的膜源，而微管相关蛋白1轻链3脂化是自噬体生物生成的关键步骤。cGAMP诱导微管相关蛋白1轻链3脂化的途径依赖于结合蛋白WD重复结构域磷酸肌醇互作蛋白2和自噬相关基因5，但独立于自噬相关蛋白ULK和VPS34-beclin激酶复合物。此外，他们还发现cGAMP诱导的自噬对清除细胞质中的DNA和病毒非常重要。 TBK1文献共被引聚类分析图(图8)中发现有244个节点、250条连线。Modularity Q=0.873 3 > 0.3，这表明该聚类图具有合理性。Weighted Mean Silhouette S=0.965 7 > 0.5这代表同质性也是合理的。在这些共被引文献中，相似的文献会被归为同一个聚类中，并用一个聚类标签表示。在这个聚类图中，主要的聚类如下：#0 amyotrophic lateral sclerosis(肌萎缩侧索硬化)；#1cyclic gmp-amp synthase(环状GMP-AMP合成酶)；#2 selective autophagy(选择性自噬)；#3 sting(干扰素基因刺激蛋白)；#4 innate immunity(天然免疫)；#5 optineurin(选择性自噬受体)；#6 cgas-sting(cGAS-STING 信号通路)；#7 macrophages(巨噬细胞)；#8 gene expression(基因表达)；#9 cell signaling(细胞信号)；#10 tumor immunotherapy(肿瘤免疫治疗)；#11 nomogram(诺谟图)；#12 tank-binding kinase 1(TBK1)；#13 cGAMP(环二核苷酸)；#14 african swine fever virus(非洲猪瘟病毒)；#15 obesity(肥胖症) #16 irf(干扰素调节因子)。 2.6 TBK1文献关键词分析关键词作为一篇文章的精髓，能够快速准确地反映一篇文章的研究主题。关键词的出现频次、突现强度以及关键词时间轴共同反映了某领域某时间段的研究热点。结合高共被引文献的内容、共被引文献聚类分析结果、关键词共现图(图9)，总结出TBK1领域的研究热点包括TBK1在先天免疫系统中的作用、cGAS-STING-TBK1信号通路或TBK1与NF-κB的上下游关系、TBK1基因在肌萎缩侧索硬化的作用、TBK1与开角型青光眼的相关研究和TBK1因子的激活途径与表达等。许多高频次关键词如innate immune response、innate immunity、nf kappa b、activation、recognition、expression等在2015年已经是高频次关键词，且这些关键词热度甚至持续到2025年(图10)。 "

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