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. 2021 Sep 7;118(37):e2021013118. doi: 10.1073/pnas.2021013118

Fig. 7.

Fig. 7.

An FGF-2 signaling pathway promotes intramuscular adipogenesis in the aged skeletal muscle. Binding of fibroblast growth factor-2 (FGF-2) phosphorylates the intracellular tyrosine kinase domain of fibroblast growth factor receptor (FGFR), which activates intracellular signaling pathways including MAPK/ERK kinase 1/2 (MEK1/2) to phosphorylate extracellular signal-regulated kinases (ERK1/2; p44/42 MAPK). MAPK activity increases both the abundance of Fosl1 and transactivating capacities of the Fos–Jun heterodimer. Phosphorylation of Fos-related antigen (FRA-1) enhances its binding to the activator protein-1 (AP-1) DNA-binding site located in the miR-29a promoter to stimulate transcription. In the aged skeletal muscle, enhanced FGF-2 signaling increases phosphorylated FRA-1 levels, which in turn promote miR-29a expression. Enhanced miR-29a levels stimulate differentiation of FAPs into adipocytes via the reduction of SPARC, promoting IMAT formation.