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转录组分析以探索下调TNIK影响RISPERIDONE作用的机制

Ruixue Yuan¹, Yaojing Li², Xiangyi Li³

¹Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Frontiers in pharmacology

|September 13, 2024

概括

里斯佩里治疗会影响骨代谢途径,可能导致骨质疏松症. 下调Traf2和Nck相互作用蛋白激酶 (TNIK) 影响原蛋白和PI3K-Akt信号传递,揭示了对RISPERIDONE的新见解.

科学领域:

神经药理学神经药理学
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

里斯佩里是治疗精神分裂症的有效抗精神病药物,但其作用机制尚未完全理解.
Traf2和Nck相互作用蛋白激酶 (TNIK) 是一种精神分裂症易感基因,与RISPERIDONE治疗反应有关.
之前的研究证实了TNIK下调会影响RISPERIDONE的下游目标.

研究的目的:

探索下调TNIK对RISPERIDONE诱导的分子表达的作用.
确定受RISPERIDONE和TNIK影响的分子通路和基因.
调查瑞斯佩里不良影响背后的潜在机制.

主要方法:

用Risperidone和TNIK siRNA治疗的U251细胞的转录组分析.
查差异表达基因 (DEGs) 和与精神分裂症相关基因交叉.
基因本体学 (GO),KEGG通路分析,以及使用STRING和Cytoscape的蛋白质-蛋白质相互作用 (PPI) 网络构建.

主要成果:

里斯佩里治疗显著丰富了与副甲状腺激素合成,分泌和作用相关的途径.
下调的TNIK影响了含有原的细胞外基质,信号受体激活器活性和PI3K-Akt通路.
骨矿化和信号通路被交叉通话基因丰富,FGFR2,FGF1和FGFR作为潜在的TNIK目标.

结论:

里斯佩里主要影响骨代谢途径,这表明与骨质疏松症风险的联系.
这项研究为RISPERIDONE的不良影响机制提供了新的视角.
了解TNIK的作用可能会导致减轻RISPERIDONE引起的副作用的策略.

关键词:

在Traf2和Nck相互作用的蛋白激酶 (TNIK) 中.骨矿化骨矿化骨矿化骨矿化蛋白质与蛋白质的相互作用里斯佩里胺的使用方法转录组分析转录组分析

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