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. 2019 Jan 7;9:1520. doi: 10.3389/fphar.2018.01520

FIGURE 3.

FIGURE 3

Rapamycin inhibits the de-differentiation of vascular smooth muscle cells. Rapamycin suppresses the de-differentiation of vascular smooth muscle cells by inhibiting the activation of mTOR and S6K1, activating PI3K/AKT pathways, inhibiting PDGF pathway and the formation of FGFR-1/FRS2/mTOR complex. In addition, rapamycin inhibits the synthesis of hyaluronan through decreasing HAS and the secretion of VEGF. The solid lines with arrow and notation ↑ indicate increase or activation, and lines without arrows indicate decrease or suppression. VSMC, vascular smooth muscle cell; S6K1, ribosomal protein S6 kinase 1; mTOR, mammalian target of rapamycin; IFN-γ, interferon-γ; IL-1β, interleukin-1β; VEGF, vascular endothelial growth factor; RAPA, rapamycin; HAS, hyaluronan synthase; α-SMA, α-smooth muscle actin; SM-MHC, smooth muscle-myosin heavy chain; FGFR1, fibroblast growth factor receptor 1; FRS2, fibroblast growth factor receptor substrate 2; FGF, fibroblast growth factor; IGF, insulin-like growth factor; PDGF, platelet-derived growth factor.