Role of histone acetylation in the pathogenesis of IgA nephropathy / 上海交通大学学报（医学版）

ABSTRACT

Objective: To study the role of abnormal histone acetylation modification in the pathogenesis of IgA nephropathy (IgAN), and explore the pathogenesis of IgAN from the perspective of epigenetics. Methods: 30 patients with primary IgAN and 19 healthy controls were included. Of the 19 controls, 16 cases were used to collect blood samples and 3 cases were used to collect normal renal tissues. Peripheral venous blood was collected to extract mononuclear cells (PBMC) for detection. The levels of histone H3 and H4 acetylation in PBMC of IgAN group and healthy control group were detected by ELISA. Real-time PCR was used to detect the mRNA expressions of P300, CREBBP, HDAC1-3, HDAC7, HDAC8, C1GALT1 and ST6GALNAC2. The acetylation levels of histone H3 and H4 in promoter regions of C1GALT1 and ST6GALNAC2 were detected by chromatin immuneprecipitation (CHIP). The protein expression of HDAC1 and H3Ac was detected by immunofluorescence. T-test was used for statistical analysis. Results: Compared with the healthy control group, the acetylation levels of H3 and H4 in IgAN group were significantly higher than those in healthy control group (P=0.035, P=0.012);the mRNA expressions of P300, CREBBP, HDAC1, HDAC8 and ST6GALNAC2 were significantly increased in IgAN group (P=0.002, P=0.001, P=0.001, P=0.045 P=0.012); the mRNA expressions of HDAC2 and C1GALT1 were decreased significantly (P=0.035, P=0.008); the acetylation degree of H3 and H4 in C1GALT1 promoter region was significantly decreased (P=0.043, P=0.005), the degree of H3 and H4 acetylation in the promoter region of ST6GALNAC2 gene was increased significantly in IgAN group (P=0.038, P=0.021);immune fluorescent results of renal tissue indicated that the HDAC1 protein expression was increased obviously, and H3Ac protein expression was significantly reduced in the renal tissue of IgAN patiegts. Conclusion: Abnormal acetylation modification exists in IgAN patients. Histone acetylation modification may participate in the pathogenesis of IgAN by regulating the expression of glycosylase gene.