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Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney.

Cai, Mengyin; Pradeep, Bompada LU ; Grubich Atac, David LU ; Laakso, Markku; Groop, Leif LU and De Marinis, Yang LU (2016) In Biochemical and Biophysical Research Communications 469(1). p.108-113
Abstract
Diabetes nephropathy (DN) is the leading cause of end stage renal disease and it affects up to 40% of diabetic patients. In addition to hyperglycemia, genetic factors are thought to contribute to the development of DN, but few if any genetic factors have been convincingly linked to DN. Other possible mechanisms may involve epigenetic regulation of glucose-stimulated gene activity which was suggested to explain long-term effects of poor glycemic control on risk of diabetic complications, often referred to as metabolic memory. Osteopontin (OPN) is one of the genes upregulated in kidneys from diabetic mouse models as well as humans with DN, and suggested to play an important role in the pathogenesis of DN. In this study, we demonstrated that... (More)
Diabetes nephropathy (DN) is the leading cause of end stage renal disease and it affects up to 40% of diabetic patients. In addition to hyperglycemia, genetic factors are thought to contribute to the development of DN, but few if any genetic factors have been convincingly linked to DN. Other possible mechanisms may involve epigenetic regulation of glucose-stimulated gene activity which was suggested to explain long-term effects of poor glycemic control on risk of diabetic complications, often referred to as metabolic memory. Osteopontin (OPN) is one of the genes upregulated in kidneys from diabetic mouse models as well as humans with DN, and suggested to play an important role in the pathogenesis of DN. In this study, we demonstrated that OPN gene expression is upregulated in the kidneys of a hyperglycemia diabetes mouse model SUR1-E1506K, and glucose-stimulated OPN gene expression is strongly associated with increases in activating histone marks H3K9ac, H3K4me1 and H3K4me3 and decrease in inactivating mark H3K27me3 in the promoter region of OPN gene. These findings were replicated in human mesangial cells treated with high glucose. Further proof for the involvement of histone acetylation and methylation in glucose-induced changes in OPN gene expression was obtained by manipulating histone modifications thereby OPN gene expression by histone deacetylase (HDAC) inhibitor trichostatin A and histone methyltransferase (HMT) inhibitor MM-102. We conclude that glucose is a potent inducer of histone acetylation and methylation, which in turn leads to upregulation of OPN gene expression. Treatment targeting histone marks may therefore represent an alternative method to protect kidneys from deleterious effects of glucose. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
469
issue
1
pages
108 - 113
publisher
Elsevier
external identifiers
  • pmid:26592666
  • wos:000368868000017
  • scopus:84950280045
ISSN
1090-2104
DOI
10.1016/j.bbrc.2015.11.079
language
English
LU publication?
yes
id
6b10ffc8-ad8f-467a-ab85-4a6cb4ec6803 (old id 8234906)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26592666?dopt=Abstract
date added to LUP
2015-12-06 12:16:33
date last changed
2017-06-25 03:02:57
@article{6b10ffc8-ad8f-467a-ab85-4a6cb4ec6803,
  abstract     = {Diabetes nephropathy (DN) is the leading cause of end stage renal disease and it affects up to 40% of diabetic patients. In addition to hyperglycemia, genetic factors are thought to contribute to the development of DN, but few if any genetic factors have been convincingly linked to DN. Other possible mechanisms may involve epigenetic regulation of glucose-stimulated gene activity which was suggested to explain long-term effects of poor glycemic control on risk of diabetic complications, often referred to as metabolic memory. Osteopontin (OPN) is one of the genes upregulated in kidneys from diabetic mouse models as well as humans with DN, and suggested to play an important role in the pathogenesis of DN. In this study, we demonstrated that OPN gene expression is upregulated in the kidneys of a hyperglycemia diabetes mouse model SUR1-E1506K, and glucose-stimulated OPN gene expression is strongly associated with increases in activating histone marks H3K9ac, H3K4me1 and H3K4me3 and decrease in inactivating mark H3K27me3 in the promoter region of OPN gene. These findings were replicated in human mesangial cells treated with high glucose. Further proof for the involvement of histone acetylation and methylation in glucose-induced changes in OPN gene expression was obtained by manipulating histone modifications thereby OPN gene expression by histone deacetylase (HDAC) inhibitor trichostatin A and histone methyltransferase (HMT) inhibitor MM-102. We conclude that glucose is a potent inducer of histone acetylation and methylation, which in turn leads to upregulation of OPN gene expression. Treatment targeting histone marks may therefore represent an alternative method to protect kidneys from deleterious effects of glucose.},
  author       = {Cai, Mengyin and Pradeep, Bompada and Grubich Atac, David and Laakso, Markku and Groop, Leif and De Marinis, Yang},
  issn         = {1090-2104},
  language     = {eng},
  number       = {1},
  pages        = {108--113},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2015.11.079},
  volume       = {469},
  year         = {2016},
}