Overexpression of Nrf2 in Renal Proximal Tubular Cells Stimulates Sodium–Glucose Cotransporter 2 Expression and Exacerbates Dysglycemia and Kidney Injury in Diabetic Mice
نویسندگان
چکیده
We investigated the impact of nuclear factor erythroid 2–related 2 (Nrf2) overexpression in renal proximal tubular cells (RPTCs) on blood glucose, kidney injury, and sodium–glucose cotransporter (Sglt2) expression diabetic Akita Nrf2−/−/Nrf2RPTC transgenic (Tg) mice. Immortalized human RPTCs (HK2) stably transfected with plasmid containing SGLT2 promoter kidneys from patients diabetes were also studied. Nrf2 was associated increased glomerular filtration rate, urinary albumin-to-creatinine ratio, tubulointerstitial fibrosis, Sglt2 Tg mice compared their Nrf2−/− littermates. In vitro, oltipraz or transfection NRF2 cDNA stimulated activity HK2, these effects inhibited by trigonelline siRNA. The deletion NRF2-responsive element (NRF2-RE) abolished stimulatory effect activity. binding to NRF2-RE confirmed gel mobility shift assay chromatin immunoprecipitation assays. Kidneys exhibited higher levels than without diabetes. These results suggest a link which mediates hyperglycemia stimulation exacerbates glucose injury
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ژورنال
عنوان ژورنال: Diabetes
سال: 2021
ISSN: ['1939-327X', '0012-1797']
DOI: https://doi.org/10.2337/db20-1126