The role of transcription factor Ap1 in the activation of the Nrf2/ARE pathway through TET1 in diabetic nephropathy
Autor: | Qingfei Li, Huaimin Cao, Yongshun Tan, Jianjun Sun |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male NF-E2-Related Factor 2 Upstream and downstream (transduction) Inflammation Diabetes Mellitus Experimental Dioxygenases Diabetic nephropathy Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Fibrosis medicine Animals Humans Diabetic Nephropathies Transcription factor Cells Cultured Messenger RNA Microarray analysis techniques business.industry Cell Biology General Medicine medicine.disease Rats Transcription Factor AP-1 AP-1 transcription factor 030104 developmental biology 030220 oncology & carcinogenesis Cancer research medicine.symptom business Signal Transduction |
Zdroj: | Cell biology internationalREFERENCES. 45(8) |
ISSN: | 1095-8355 |
Popis: | 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. 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. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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