Fig. 2.

Endogenous factors regulating sirtuin-1 in diabetic nephropathy. A reduction in the NAD+/NADH ratio induced by higher Nampt expression and the metabolism of glucose and fatty acids causes a downregulation of sirtuin-1 during diabetes. Low expression of hnRNP F in diabetes downregulates sirtuin-1 transcription. High expression of miR-34a-5p, miR-377, and miR-155-5p suppresses sirtuin-1 levels by directly targeting its 3’-untranslated region. Upregulation of miR-34a-5p and miR-217 expression is negatively correlated with sirtuin-1 expression in diabetic nephropathy. Diabetes-induced DNA damage promotes the expression and activity of p53, which induces miR-155-5p expression and inhibits sirtuin-1 expression. Downregulation of AMPK decreases the NAD+ concentration and consequently the expression of sirtuin-1