FGFR2-IIIb D3 extracellular domain inhibits lipid synthesis in keratinocytes |
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Authors: | XIE Ying LIU Ge WANG Ju |
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Institution: | Institute of Biomedicine, Jinan University, Guangzhou 510632, China |
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Abstract: | AIM:To investigate the inhibitory effect of extracellular domain of fibroblast growth factor receptor 2 (FGFR2)-Ⅲb D3 on lipid synthesis in HaCaT keratinocyteas. METHODS:The bioactivity of FGFR2-Ⅲb D3 extracellular domain was detected by isothermal titration calorimetry (ITC) and CCK-8 assay. The inhibitory effect of FGFR2-Ⅲb D3 extracellular domain on lipid synthesis in HaCaT cells was analyzed by real-time PCR, Western blot, flow cytometry and oil red O staining. RESULTS:The results of ITC, real-time PCR and CCK-8 assay showed that FGFR2-Ⅲb was highly expressed in HaCaT cells, and FGFR2-Ⅲb D3 extracellular domain specifically bound to FGF7 to inhibit HaCaT cell viability. The results of real-time PCR and Western blot showed that FGF7 significantly up-regulated the mRNA expression of sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA synthase (ACS), stearoyl-CoA desaturase (SCD) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and the protein levels of p-FGFR, p-AKT and SREBP-1 in HaCaT cells, and these effects were inhibited after the treatment with FGFR2-Ⅲb D3 extracellular domain and AKT inhibitor, which was significantly different from the FGF7 group. and The results of oil red O staining and flow cytometry showed that the lipid content of HaCaT cells was increased after FGF7 induction. After treatment with FGFR2-Ⅲb D3 extracellular domain and AKT inhibitor, the lipid content was decreased (P<0.01). CONCLUSION:FGFR2-Ⅲb D3 extracellular domain inhibits the autophosphorylation of FGFR2-Ⅲb by its competitive binding to FGF7, and then blocks downstream PI3K-AKT signaling pathway, thus resulting in the down-regulation of SREBP-1c and downstream lipid synthases, and inhibiting lipid synthesis in keratinocytes. |
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Keywords: | FGFR2-IIIb D3 extracellular domain Fibroblast growth factor 7 Sterol regulatory element bin-ding protein-1c Lipid synthesis Keratinocytes |
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