Relationship between histone acetylation modification in spleen CD4+T cells and diabetic nephropathy of nonobese diabetic mice

Abstract

To explore the relationship between histone acetylation modification in spleen CD4+T cells and diabetic nephropathy. Non-obese diabetic (NOD) mice were randomly divided into 4 groups and random blood glucose at 12, 18, 24 and 30 weeks were detected. Urinary albumin and creatinine were detected by enzyme-linked immunosorbent assay (ELISA). The global acetylation levels of H3 and H4 in CD4+T cells were measured by H3/H4 acetylation kit. The relevant mRNA expression level of histone acetylation modification enzymes was detected by real-time quantitative polymerase chain reaction (PCR) and the altered expression genes verified by Western blot. Compared with mice from 12 weeks, there were significant increases in blood glucose levels and urinary albumin/creatinine ratio (ACR) from 24 and 30 weeks (glucose: (18.1±6.3) and (20.7±7.5) vs (7.2±3.1) mmol/L, ACR: (4.04±1.54) and (8.11±1.77) vs (2.12±0.56) mg/g). Conversely, the global acetylation levels of H3 (0.068±0.023 and 0.043±0.017 vs 0.127±0.036) and H4 (0.058±0.022 and 0.041±0.019 vs 0.082±0.032) in spleen CD4+T cells from 24 and 30 weeks were obviously lower. The mRNA levels of such histone acetylases as P300 (15.53±6.31 and 13.76±3.62 vs 22.94±7.40) and P300/CBP-associated factor (PCAF) (3.21±0.81 and 2.74±0.36 vs 5.31±0.73) declined while the protein and mRNA of histone deacetylase 5 (HDAC5) significantly increased from 24 and 30 weeks. All the above differences were statistically significant (P<0.05). The levels of H3 (r=-0.590, P=0.043) and H4 (r=-0.702, P=0.011) were negatively correlated with urinary ACR while HDAC5 level was positively correlated with urinary ACR from 24 and 30 weeks (r=0.673, P=0.016). With aging and progression of nephropathy in NOD mice, the global acetylation levels of H3 and H4 decrease while the expression level of HDAC5 increases in spleen CD4+T cell. And altered HDAC5 expression in spleen CD4+T cells is closely correlated with kidney damage in NOD mice.