Fig. 2

The signal molecules modulated by IGFBP7 and MMRN2. The red icons represent the signal molecule regulated by MMRN2, and the purple icons represent the signaling molecules regulated by IGFBP7. 1). IGFBP7 promoted TGF-1R and AKT phosphorylation and activated the p38MAPK pathway, upregulating p53, p27Kip1, and p21Cip1. 2). IGFBP7 inhibited AKT and MPK3 activity, MEK and ERK1/2 phosphorylation, and COX-2 and VEGF mRNA expression. IGFBP7 interrupts the IGF1R-IGF1/2 interaction and, in turn, inhibited the downstream PI3K-AKT pathway. 3) TGF-β1 induced by TGF-β1/ALK5/Smad-2 and VEGF induced IGFBP7 expression. MKP3 could inhibit IGFBP7 expression. IGFBP7 transcriptional activation required Smarcb1 participation, while Smarcb1 inhibited AKT activation. 4) MMRN2 inhibited p38 activation and Src, VEGFR2, and VE-cadherin phosphorylation. 5) MMRN2 downregulated VEGFR1, VEGFR2, Tie2, MLC2, Apelin, and Ang-2. 6) MMRN2 upregulated VE-cadherin, β-catenin, ZO-1, and JAM-A, MMRN2 upregulated some cytokines, such as Ang2, PDGF, and HB-EGF, and 7) VEGFF-A could downregulate MMRN2.

Alt Text: There is a connected cell in the figure in which the intrinsic pathways involved in the relevant molecules are marked