Gene Expression Profiling of Multiple Histone Deacetylases () and Its Correlation with -Mediated Redox Regulation in the Pathogenesis of Diabetic Foot Ulcers.

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein of the leucine zipper family, which mitigates inflammation and employs cytoprotective effects. Attempting to unravel the epigenetic regulation of type 2 diabetes mellitus (T2DM) and diabetic foot ulcer (DFU), we profiled the expression of eleven isoform-specific histone deacetylases () and correlated them with and cytokines. This study recruited a total of 60 subjects and categorized into DFU patients ( = 20), T2DM patients ( = 20), and healthy controls ( = 20). The DFU patients were subcategorized into uninfected and infected DFU ( = 10 each). We observed a progressive decline in the expression of and its downstream targets among T2DM and DFU subjects. The inflammatory markers and were significantly upregulated, whereas anti-inflammatory marker was significantly downregulated in DFU. Of note, a significant upregulation of and downregulation of among DFU patients were observed. The significant positive correlation between and in DFU patients suggested the vital role of in redox homeostasis and angiogenesis. In contrast, the significant negative correlation between and , and , implied an imbalance in circuit. Furthermore, a significant positive correlation was observed between and and the negative correlation between and suggested the pro-inflammatory role of and the anti-inflammatory role of in signaling. In conclusion, the epigenetic changes such as upregulation of and downregulation of and their association with as well as inflammatory markers are suggestive of their roles in pathophysiology of T2DM and DFU.