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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Lab Invest. 2014 Mar 10;94(5):503–516. doi: 10.1038/labinvest.2014.42

Figure 11. A simplified model of the mechanism of AGEs in the divergent regulation of gene expression of RAGE and AGE-R1 in HSC, which is eliminated by curcumin.

Figure 11

The interaction of AGEs with RAGE induces gene expressions of leptin and its receptor, leading to the activation of leptin signaling, including JAK2 and PI3K. The latter suppresses the activity of Nrf2 and gene expression of GCL and its activity, leading to the reduction in cellular GSH and the elevation of oxidative stress. The latter facilitates the divergent regulation of gene expression of RAGE and AGE-R1. The elevated abundance of RAGE shows a positive feedback mechanism and, in turn, enhances its interaction with AGEs and the subsequent events, collectively leading to the activation of HSC. Curcumin interrupts leptin signaling and blocks the occurrences of the subsequent events, resulting in the elimination of the effects of AGEs and the inhibition of HSC activation. “↑” or “↓” indicates the effects of AGEs. “⊢” represents the inhibitory role of curcumin in the process.