Foxc2 Alleviates Ox-LDL-Induced Lipid Accumulation, Inflammation, and Apoptosis of Macrophage via Regulating the Expression of Angptl2.

Liu Yang, Tie Li, Lihuang Zha

Inflammation 2020 Aug

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The present study aimed to investigate the role of Forkhead box protein C2 (Foxc2) in oxidized low-density lipoprotein (ox-LDL)-induced macrophages and identify the potential mechanisms. RAW264.7 cells, the murine macrophage cell line, were stimulated by ox-LDL, and cell proliferation was examined. The levels of inflammation- and oxidative stress-related markers were detected using kits after induction with ox-LDL. Subsequently, the expression of Foxc2 was measured using Western blotting. After transfection with Foxc2 pcDNA3.1, intracellular lipid droplets were examined using oil red O staining. The levels of total cholesterol (TC), free cholesterol (FC), inflammatory cytokines, and oxidative stress markers were determined. Moreover, apoptosis of RAW264.7 cells was detected using flow cytometry, and apoptosis-related proteins were measured using Western blotting. Angiopoietin-like protein 2 (Angptl2) was predicted as a target gene of Foxc2. Therefore, the expression of Angptl2 was examined after Foxc2 overexpression in ox-LDL-induced RAW264.7 cells. Then, the changes of intracellular lipid droplets, TC, FC, inflammatory cytokines, oxidative stress factors, and cell apoptosis were detected after Angptl2 overexpression or co-transfection with Foxc2 and Angptl2 pcDNA3.1. The results revealed that ox-LDL induction inhibited proliferation of RAW264.7 cells and promoted the release of inflammatory factors. Importantly, the expression of Foxc2 was obviously decreased after stimulation by ox-LDL. Foxc2 overexpression suppressed lipid accumulation, TC, FC levels, inflammation, oxidative stress, and apoptosis induced by ox-LDL, whereas these inhibitory effects were relieved after co-transfection with Angptl2 pcDNA3.1. These findings demonstrated that Foxc2 can alleviate ox-LDL-induced lipid accumulation, inflammation, and apoptosis of macrophage via regulating the expression of Angptl2.

Citation

Liu Yang, Tie Li, Lihuang Zha. Foxc2 Alleviates Ox-LDL-Induced Lipid Accumulation, Inflammation, and Apoptosis of Macrophage via Regulating the Expression of Angptl2. Inflammation. 2020 Aug;43(4):1397-1410