Epigenetic regulation of the thioredoxin-interacting protein (TXNIP) gene by hyperglycemia in kidney.
Författare
Summary, in English
Diabetic kidney disease is the leading cause of end-stage renal disease. Genetic factors have been suggested to contribute to its susceptibility. However, results from genetic studies are disappointing possibly because the role of glucose in diabetic kidney disease predisposed by epigenetic mechanisms has not been taken into account. Since thioredoxin-interacting protein (TXNIP) has been shown to play an important role in the pathogenesis of diabetic kidney disease, we tested whether glucose could induce expression of TXNIP in the kidney by epigenetic mechanisms. In kidneys from diabetic Sur1-E1506K(+/+) mice, hyperglycemia-induced Txnip expression was associated with stimulation of activating histone marks H3K9ac, H3K4me3, and H3K4me1, as well as decrease in the repressive histone mark H3K27me3 at the promoter region of the gene. Glucose also coordinated changes in histone marks and TXNIP gene expression in mouse SV40 MES13 mesangial cells and the normal human mesangial cell line NHMC. The involvement of histone acetylation in glucose-stimulated TXNIP expression was confirmed by reversing or enhancing acetylation using the histone acetyltransferase p300 inhibitor C646 or the histone deacetylase inhibitor trichostatin A. Thus, glucose is a potent inducer of histone modifications, which could drive expression of proinflammatory genes and thereby predispose to diabetic kidney disease.
Avdelning/ar
- EXODIAB: Excellence of Diabetes Research in Sweden
- Translationell Muskel Forskning
- Diabetiska komplikationer
- Klinisk patologi, Malmö
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2016
Språk
Engelska
Sidor
342-353
Publikation/Tidskrift/Serie
Kidney International
Volym
89
Issue
2
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Urology and Nephrology
Status
Published
Forskningsgrupp
- Genomics, Diabetes and Endocrinology
- Diabetic Complications
- Clinical pathology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1523-1755