Effection Of FGF21on Expression And Regulation Of ABCA1and ABCG1in THP-1Macrophage-derived Foam Cells

Objectives:This project is to work on human THP-1macrophage-derived foamcells. Here, we try to investigate the effects of fibroblast growth factor21(FGF21) on the expression of ATP binding cassette transporter A1and G1(ABCA1/G1) and cholesterol efflux, and to investigate the role of theupstream regulatory factor-liver X receptor alpha (LXRα). Thus, weexplore the effect and potential mechanism of FGF21to inhibitatherogenesis.Methods:1. The THP-1macrophage-derived foam cells were exposed to FGF21of different concentrations (10,50,100ng/ml). Then, total RNA andprotein of foam cells were isolated;2. The mRNA expression of ABCA1, ABCG1and LXRα weredetermined by real-time quantitative PCR;3. The protein expression of ABCA1, ABCG1and LXRα weredetermined by Western blot; 4. The cholesterol efflux were analyzed by liquid scintillation counter;5. Furthermore, Short-interfering RNA (siRNA) of LXRα was used.Then，the foam cells were exposed to FGF21at100ng/ml. With the samemethods above, the effects of FGF21on the expression of ABCA1andABCG1and cholesterol efflux were determined.Results:1. Detected by RT-qPCR, FGF21increased the mRNA expression ofABCA1, ABCG1and LXRα, and these effects were dose-dependent;2. Detected by Western blot, FGF21increased the protein expressionof ABCA1, ABCG1and LXRα, and these effects were dose-dependent;3. Detected by liquid scintillation counter, FGF21increased thecholesterol efflux from foam cells, and this effect were dose-dependent;4. LXRα-siRNA attenuated the stimulatory effects of increasedcholesterol efflux and expression of ABCA1, ABCG1and LXRα inducedby FGF21.Conclusions:FGF21increased the expression of ABCA1and ABCG1and enhancedcholesterol efflux in the THP-1macrophage-derived foam cells, which wasmediated by LXRα signaling pathway.