Metformin Corrects Rage Overexpression Caused Signaling Dysregulation And Nf-Kappa B Targeted Gene Change

Background: Advanced glycation end products, known as AGEs, are substances that can be a factor in the development or worsening of many degenerative diseases, such as diabetes. The negative effect of AGEs has been noticed and studied on human keratinocytes but it is still poorly understood about the effect of diabetic drug on AGE caused skin damage despite the skin complications are critical problem of long course diabetes. Materials and methods: In order to study the effect of diabetic drug metformin on AGEs caused signaling dysregulation on human keratinocytes, we used lentiviral vector to overexpress the receptor for advanced glycation end products (RAGE) in immortalized human keratinocytes (HaCaT cells). Results: We showed that phosphorylation of p38, ERK1/2, JNK and Akt was dysregulated and all of them were corrected by metformin treatment. Moreover, the expressions of NF-kBp65 and downstream factors ICAM1, TNF-alpha, Cox-2, IL-6, and IL-1 beta were also changed, in which the expression of those were rectified by metformin. Conclusions: This study is the first to show the therapeutic effects of diabetic drug metformin on AGEs caused signaling dysregulation on human keratinocytes.