Abstract
TET1 mediates demethylation in tumors, but its role in diabetic nephropathy (DN), a prevalent diabetic complication, is unclear. We attempted to probe the possible mechanism of TET1 in DN. A DN rat model was established and verified by marker detection and histopathological observation. The in vitro model was established on human mesangial cells (HMCs) induced by high glucose (HG), and verified by evaluation of fibrosis and inflammation. The differentially expressed mRNA was screened out by microarray analysis. The most differentially expressed mRNA (TET1) was reduced in DN rats and HG-HMCs. The upstream and downstream factors of TET1 were verified, and their roles in DN were analyzed by gain- and loss-function assays. TET1 was decreased in DN rats and HG-HMCs. High expression of TET1 decreased biochemical indexes and renal injury of DN rats and hampered the activity, fibrosis, and inflammation of HG-HMCs. Ap1 lowered TET1 expression, and enhanced inflammation in HG-HMCs, and accentuated renal injury in DN rats. TET1 overexpression inhibited the effect of Ap1 on DN. TET1 promoted the transcription of Nrf2. The Ap1/TET1 axis mediated the Nrf2/ARE pathway activity. Overall, TET1 overexpression weakened the inhibitory effect of Ap1 on the Nrf2/ARE pathway, thus alleviating inflammation and renal injury in DN.