CpG array analysis of histone H3 lysine 4 trimethylation in patients with IgA nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the aberrance of histone H3 lysine 4 trimethylation (H3K4me3) in patients with IgA nephropathy (IgAN).</p><p><b>METHODS</b>In 15 patients with IgAN and 15 healthy volunteers, H3K4me3 variations in peripheral blood mononuclear cells (PBMCs) were analyzed using chromatin immunoprecipitation and microarray analysis (ChIP-chip). ChIP real-time PCR was used to validate the microarray results. Quantitative real-time PCR (qRT-PCR) was carried out to examine the correlations between the mRNA expression profiles and H3K4me3 levels.</p><p><b>RESULTS</b>We identified 83 genes that displayed significant H3K4me3 differences in IgAN patients compared with healthy subjects. Among them, 39 genes showed increased H3K4me3 and 44 genes had decreased H3K4me3 levels. The results of ChIP real-time PCR were well consistent with the microarray data. Quantitative RT-PCR revealed the correlations between the mRNA expressions and the methylation levels of H3K4me3.</p><p><b>CONCLUSION</b>IgAN patients have significant alterations in H3K4me3, and the genes with aberrant H3K4me3 may provide insights into the pathogenesis of IgAN.</p>

Expression of MMP-2 and TIMP-1 in renal tissues of patients with chronic active antibody-mediated renal graft rejection / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR.</p><p><b>METHODS</b>Immunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed.</p><p><b>RESULTS</b>The expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05).</p><p><b>CONCLUSION</b>Abnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.</p>