Potential Role of Gene Regulator NFAT5 in the Pathogenesis of Diabetes Mellitus

Figure 4

Gene and drug therapy of NFAT5 target for diabetes. Drugs (long red arrow) increase (+) or decrease (-) expression of NFAT5 mRNA and protein. Lithium inhibits phosphorylation of glycogen synthase kinase-3β (GSK-3β) and increases expression of NFAT5 rapidly, while long-term lithium exposure decreases NFAT5 expression. NFAT5 silencing RNA (siRNA) and haploinsufficiency disrupt the transcription of NFAT5. The DNA-binding activities of NFAT5 in the promoter of aldose reductase (AR) gene are significantly decreased in the presence of AR inhibitor (ARI). KRN2 and KRN5 derivate from berberine. Cerulenin, KRN2, and KRN5 selectively block NF-κB binding to the NFAT5 promoter region and inhibit transcriptional activation of NFAT5 cyclosporin A (CsA).