PTP1B磷酸化在整合素和钙黏蛋白介导的MSCs粘附中的作用与机制研究

如何提高细胞与支架材料的粘附效率是选择性细胞滞留(SCR)等生物活性材料研发的关键。由整合素-粘附斑激酶-Src-链蛋白-钙黏蛋白形成的信号体系是调控间充质干细胞（MSCs）等细胞与支架材料粘附的核心途径。研究显示，蛋白酪氨酸磷酸酶（PTP）1B对该信号通路具有相互平衡、靶点特异性的双重调节作用。据此推测，抑制PTP1B tyr 152可促进链蛋白/钙黏蛋白复合体分离，进而通过α链蛋白-肌动蛋白-细胞骨架途径增强MSCs的粘附活性。本课题拟制备PTP1B的tyr 152等结构域模拟肽，特异性调节PTP1B不同功能位点的磷酸化水平，观察其对整合素-粘附斑激酶-Src-链蛋白-钙黏蛋白信号体系的调控效应及对MSCs与基质材料粘附功能的影响。通过本研究将有助于深入阐述以MSCs为代表的细胞与基质材料的粘附机制及其调控途径，还可为SCR等相关生物活性材料的研发提供新的思路和科学依据。

How to improve the adhesion of cells and scaffold material efficiency is the key to selective cell retention (SCR) and other bioactive materials research and development. By the integrins-FAK-Src-cadherin-catenin signal system, cadherin is formed between the core pathways regulating cell adhesion and scaffolds, such as mesenchymal stem cells(MSCs). Research shows that the protein tyrosine phosphatase(PTP)1B are balanced with the signal path , the target-specific double regulation. Presumably, inhibition of PTP1B tyr 152 may promote catenin/cadherin complex separation, and then through the α-catenin-actin-cytoskeleton way to enhance adhesion activity of MSCs. The topic was to prepare the PTP1B tyr 152domains such as analog peptide-specific regulatory phosphorylation of PTP1B different functional loci observed for integrins-FAK-Src-cadherin-catenin regulation of signal system effects on the MSCs with the matrix material adhesion function . Through this study will contribute to further elaborate mechanisms to MSCs adhered cells represented with the matrix material and regulatory pathways, but also provide new ideas and scientific basis for the development of SCR and other related bioactive materials.