基于苦味受体表达的多组织细胞传感器及其应用

Multi-tissue cell sensors based on the expression of bitter taste receptors and their application

非口腔组织中的苦味受体(TAS2Rs)可能成为相关疾病治疗的新靶点。该研究将表达有TAS2Rs的细胞作为敏感元件,根据其生理特性与不同的传感器耦合,探究了味觉受体异位表达及其在个性化药物筛选中的应用,构建了针对不同疾病模型的个性化药物筛选平台。首先,基于细胞阻抗传感器以及内源性表达TAS2R38受体的结肠癌细胞,开发了异硫氰酸酯类物质特异性药物筛选平台,求得苯硫脲的EC50为157.6μM;其次,结合微电极阵列检测系统,探究了TAS2Rs激动剂地芬尼多(5~160μM)和水杨苷(0.001~100μM)对心肌细胞收缩的抑制作用;此外,基于3D呼吸道平滑肌细胞(ASMCs)阵列,结合凝胶成像系统,探究了TAS2Rs激动剂桔皮素(20μM)对呼吸道平滑肌细胞的舒张作用。

The TAS2 Rs in extra-oral tissues may become a potential therapeutic target in the treatment of related diseases.In this study,cells expressing of TAS2 Rs are used as sensitive elements.According to their physiological characteristics and coupling with different sensors,the heterotopic expression of taste receptors and their application in personalized drug screening are explored.The personalized drug screening platform for different disease models is established.Firstly,based on the electric cell-substrate impedance sensing(ECIS)and the endogenous T2 R38 receptor expressing Caco2 cells,a drug screening platform for isothiocyanates is developed.The EC50 of phenylthiourea is calculated as 157.6μM.Secondly,combined with the microelectrode array(MEA)detection system,the inhibitory effects of diphenidol(5~160μM)and salicin(0.001~100μM)on the contraction of cardiomyocytes are investigated.Furthermore,based on three-dimensional airway smooth muscle cells(ASMCs)array and the gel imaging system,the diastolic effect of tangeretin(20μM)on airway smooth muscle cells is explored.