| Fibroblast growth factors(FGFs)activate cellular signal transduction through its receptors,FGFR1,FGFR2,FGFR3 or FGFR4,regulating cellular behaviors such as migration,wound healing,proliferation,anti-apoptosis,maintenance of self-renewal,drug resistance,and angiogenesis.The regulation of cell behavior by FGFs has become a research hotspot.However,highly FGFs synthesis cost,lowly thermal stability,hardly to store,so the research work is full of challenges.Functional oligonucleotide,such as nucleic aptamer,has many advantages,such as specific recognition,highly affinity,lowly synthesis cost,highly thermal stability.In this study,we used DNA nanotechnology and the specific aptamer against FGFR1 to construct DNA-based receptor agonsit to activate receptor signaling pathways and regulate cell behavior.The FGFR receptor itself is not self-activated but requires ligand-driven receptor dimerization and subsequent trans-autophosphorylation of the cytoplasmic receptor tyrosine kinase domain.b FGF was used as a wild type Ligand,tyrosine kinase receptor FGFR was used as a model receptor,and FGFR1 agonists based on DNA strand were used as a chemical activator of FGFR1 receptor.They were applied to mouse or human derived chondrocytes,neural precursor cells,and hepatocytes.The results showed that FGFR1-agonists dimerized FGFR1 receptors to induce autophosphorylation of FGFR1 and activate downstream ERK signaling.The phenotypic study revealed that FGFR1-agonists promoted the migration and wound healing of Chondrocytes but did not affect the proliferation of chondrocytes.The results suggested that FGFR1-agonists,similarly to b FGF,systematically altered the transcriptome of the ATDC5 cells and significantly upregulated several genes,including Aven,Slc30a4,Sex and Hells.For the neural precursor cells,FGFR1-agonists could maintain multifunction and keep NPC selfrenewal undifferentiated.The universality of FGFR1-agonists provides a general strategy for biomedicine. |
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