FGF 13 functions as a regulator of the ERK/aerobic glycolysis axis in the inflammatory state during septic lung injury

Fibroblast growth factor 13 (FGF13) belongs to the FGF homologous factor subfamily, members of which lack signal peptides. In this study, we demonstrate that FGF13 is significantly downregulated in endothelial cells and macrophages in the lungs of septic patients and septic mice. However, the role of FGF13 in sepsis and the underlying mechanism are largely unknown. By using mice with conditional Fgf13 knockout and FGF13 overexpression, we find that FGF13 accelerates septic lung injury by promoting inflammatory activation of endothelial cells and macrophages. Specifically, FGF13 functions as a scaffold protein in TAK1/MEK/ERK signaling to promote hypoxia-inducible factor (HIF)−1α-regulated aerobic glycolysis in the inflammatory state. Meanwhile, the protective effect of conditional Fgf13 knockout is abolished in HIF-1α-overexpressing mice. In addition, SCH772984 (a selective antagonist of ERK signaling) abolishes the aggravation of inflammation in lungs induced by FGF13 overexpression. Our findings demonstrate that FGF13 promotes inflammatory activation upon septic lung injury through the ERK/aerobic glycolysis axis, thereby accelerating the progression of septic lung injury. FGF13 is a member of the fibroblast growth factor family and lacks a signal peptide. Here, the authors show that FGF13 is downregulated in sepsis and show in mouse models that this protein accelerates septic lung injury and promotes TAK1/MEK/ERK signalling leading to HIF1a-regulated aerobic glycolysis in the inflammatory state.