A study on mechanisms of DMBT1's regulation of occurrence and progression of chronic glomerulonephritis based on WNT signaling pathway

Objective To study the relative expression and methylation level of DMBT1 in human chronic glomerulonephritis (GGN), and to analyze the correlation of DMBT1 with the WNT/β-catenin signaling pathway in occurrence and progression of GGN.Methods The specimens of normal human kidney tissue (normal kidney tissue near the cancer tissue excised during kidney cancer surgery) from 30 cases of normal people, and damaged kidney tissue from 86 cases of GGN patients, were collected. We examined the expression of DMBT1 in the kidney tissue with GGN through real time semi-quantitative polymerase chain reaction (qRT-PCR) and western blot, and analyzed the methylation level of DMBT1 gene in the patients with GGN by methylation polymerase chain peaction (MSP). To detect the migration function of DMBT1, we selected human podocytes (HPC) and divided them into DMBT1 transfection group (to conduct over-expression of NMBT1 gene) and control group. Wound-healing assay was used to investigate migration of the cells in the two groups. Western blot was applied to explore the effect of DMBT1 on the WNT/β-catenin signaling pathway. Results DMBT1 expression was down-regulated in CGN compared with normal kidney tissues (P<0.01). Methylation PCR showed that the methylation level of DMBT1 gene was increased significantly in the GGN patients, over-expression of DMBT1 gene could inhibit cell migration and invasion (P<0.01), and after over-expression of DMBT1 gene the WNT/β-catenin signaling pathway and its downstream cytokines were suppressed obviously.Conclusions As a key regulatory factor, DMBT1 is involved in occurrence and progression of GGN by means of down-regulated methylation of DMBT1 gene.