·To study the effects of aggregated IgA1 (P-aIgA1) from patients with IgA nephropathy on the secretion of inflammatory factors and cell proliferation of human renal mesangial cells (HMCs), and observe the anti-inflammatory and anti-proliferation effects of histone deacetylation (HDAC) inhibitor sodium valproate (VPA) in vitro.

·N-IgA1 (IgA1 from health control) and P-IgA1 (IgA1 from patients with IgA nephropathy) were prepared by affinity chromatography, and P-aIgA1 and N-aIgA1 were prepared by thermal polymerization. The expression of inflammatory factors in HMCs culture supernatant was detected by human inflammatory factor protein chip. The proliferation of HMCs was detected by MTT assay. The expression of related proteins was detected by Western blotting or ELISA.

·The results of inflammatory factor protein chip showed that the concentration of interleukin-6 soluble receptor (IL-6sR), regulated upon activation normal T cell expressed and secreted factor(RANTES), tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), tumor necrosis factor-α(TNF-α) and tumor necrosis factor type Ⅱ receptor (TNFR Ⅱ) in the culture supernatant of HMCs in the P-aIgA1 group were significantly up-regulated compared with the control group, which were 34, 124, 269, 100, 1.6 and 52 times higher than those in the control group, respectively; N-aIgA1, P-IgA1 and P-aIgA1 could promote the expression of TIMP2, and there were significant differences (P=0.000, P=0.000, P=0.001). The proliferation of HMCs was observed by MTT method. The results showed that: ① Compared with the control group, N-IgA1 group had no significant effect on the proliferation of HMCs, and P-IgA1 and P-aIgA1 could significantly promote the proliferation of HMCs (P=0.045 and P=0.003); compared with the N-IgA1, HMCs in the P-aIgA1 group had significant proliferation, and the differences was statistically significant (P=0.036). ② The results of the effects of different concentrations of P-aIgA1 on the proliferation of HMCs showed that: 25 μg/mL P-aIgA1 could significantly promote the proliferation of HMCs (P=0.038), in a dose-dependent manner. ③ 400 μg/mL VPA could significantly inhibit the proliferation of HMCs (P=0.028). The effect of different IgA1 on HDAC1 in HMCs showed that the expression of HDAC1 in each group was (8.64±0.59) times (P-aIgA1), (5.42±0.16) times (P-IgA1) and (5.87±0.58) times (N-IgA1) higher than that in the control group, respectively; compared with N-IgA1, the expression of HDAC1 was significantly increased in the P-aIgA1 group (P=0.021). The effect of VPA on TNF-α secretion by mesangial cells showed that the protein expression of TNF-α in the P-aIgA1 group was significantly increased compared with the normal control group (P=0.001); compared with the P-aIgA1 group, the protein expression of TNF-α in the P-aIgA1+VPA group decreased significantly (P=0.035).

·P-aIgA1 can significantly promote the release of pro-inflammatory factors and mesangial cell proliferation, and the effect of promoting cell proliferation is concentration-dependent.Abnormal acetylation modification exists in IgA nephropathy cell model in vitro, which is involved in mesangial cell proliferation and inflammatory response. The HDAC inhibitor sodium valproate can partially reverse the above reaction. The above results suggest that sodium valproate has a certain application prospect in IgAN disease intervention, and provide a new idea for the prevention and treatment of IgA nephropathy from the perspective of epigenetics.