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

De Marinis, Yang LU ; Cai, Mengyin; Pradeep, Bompada LU ; Grubich Atac, David LU ; Kotova, Olga LU ; Johansson, Martin LU ; Garcia Vaz, Eliana LU ; Gomez, Maria LU ; Laakso, Markku and Groop, Leif LU (2016) In Kidney International 89(2). p.342-353
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Kidney International
volume
89
issue
2
pages
342 - 353
publisher
Nature Publishing Group
external identifiers
  • pmid:26806835
  • wos:000369775300014
  • scopus:84964666637
ISSN
1523-1755
DOI
10.1016/j.kint.2015.12.018
language
English
LU publication?
yes
id
b214e1b2-5f12-4b43-b2c9-434b5cb5cb91 (old id 8573817)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26806835?dopt=Abstract
date added to LUP
2016-02-04 21:08:10
date last changed
2017-05-28 04:38:59
@article{b214e1b2-5f12-4b43-b2c9-434b5cb5cb91,
  abstract     = {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       = {De Marinis, Yang and Cai, Mengyin and Pradeep, Bompada and Grubich Atac, David and Kotova, Olga and Johansson, Martin and Garcia Vaz, Eliana and Gomez, Maria and Laakso, Markku and Groop, Leif},
  issn         = {1523-1755},
  language     = {eng},
  number       = {2},
  pages        = {342--353},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Epigenetic regulation of the thioredoxin-interacting protein (TXNIP) gene by hyperglycemia in kidney.},
  url          = {http://dx.doi.org/10.1016/j.kint.2015.12.018},
  volume       = {89},
  year         = {2016},
}