Epigenetic regulation of the thioredoxin-interacting protein (TXNIP) gene by hyperglycemia in kidney.

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.

• Author: Yang De Marinis; Mengyin Cai; Bompada Pradeep; David Grubich Atac; Olga Kotova; Martin Johansson; Eliana Garcia Vaz; Maria Gomez; Markku Laakso; Leif Groop
• Department/s: EXODIAB: Excellence of Diabetes Research in Sweden; Translational Muscle Research; Diabetic Complications; Clinical pathology, Malmö; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2016
• Language: English
• Pages: 342-353
• Publication/Series: Kidney International
• Volume: 89
• Issue: 2
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26806835?dopt=Abstract; http://dx.doi.org/10.1016/j.kint.2015.12.018
• Document type: Journal article
• Publisher: Nature Publishing Group
• Topic: Urology and Nephrology
• Status: Published
• Research group: Genomics, Diabetes and Endocrinology; Diabetic Complications; Clinical pathology, Malmö
• ISBN/ISSN/Other: ISSN: 1523-1755