Research Paper Volume 13, Issue 2 pp 2982—3009

Excessive fibroblast growth factor 23 promotes renal fibrosis in mice with type 2 cardiorenal syndrome

Schematic illustration the contribution of FGF23 induced by post-infarct heart failure to promoting renal fibrosis. Myocardial infarction and heart failure up-regulates FGF23 in cardiomyocytes and increases FGF23 protein level in the kidneys through blood circulation. FGF23 binds FGFR4 in renal fibroblasts and then activates p-GSK3β/p-β-catenin/TGF-β/Vimentin/Collagen I signaling pathway to promote renal fibrosis. Intervention with FGF23 overexpression or FGFR antagonist or β-catenin inhibitor can change the degree of renal fibrosis. MI, myocardial infarction; HF, heart failure; FGF23, fibroblast growth factor 23; RBC, red blood cell; FGFR4, fibroblast growth factor receptor 4; p-GSK3β, phosphorylated glycogen synthase kinase-3 beta; p-β-catenin, phosphorylated beta-catenin; TGF-β, transforming growth factor-beta; PD173074, FGF receptor antagonist; BLU9931: FGFR4 antagonist; IGC001, β-catenin antagonist; ↑, activation; Т, inhibition.

Figure 8. Schematic illustration the contribution of FGF23 induced by post-infarct heart failure to promoting renal fibrosis. Myocardial infarction and heart failure up-regulates FGF23 in cardiomyocytes and increases FGF23 protein level in the kidneys through blood circulation. FGF23 binds FGFR4 in renal fibroblasts and then activates p-GSK3β/p-β-catenin/TGF-β/Vimentin/Collagen I signaling pathway to promote renal fibrosis. Intervention with FGF23 overexpression or FGFR antagonist or β-catenin inhibitor can change the degree of renal fibrosis. MI, myocardial infarction; HF, heart failure; FGF23, fibroblast growth factor 23; RBC, red blood cell; FGFR4, fibroblast growth factor receptor 4; p-GSK3β, phosphorylated glycogen synthase kinase-3 beta; p-β-catenin, phosphorylated beta-catenin; TGF-β, transforming growth factor-beta; PD173074, FGF receptor antagonist; BLU9931: FGFR4 antagonist; IGC001, β-catenin antagonist; ↑, activation; Т, inhibition.