Diabetes-Induced Extracellular Matrix Protein Expression Is Mediated by Transcription Coactivator p300

Kaur, Harpreet; Chen, Shali; Xin, Xiping; Chiu, Jane; Khan, Zia A.; Chakrabarti, Subrata

doi:10.2337/db06-0519

Cited by 93 publications

(137 citation statements)

References 33 publications

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“…Of note, ET-1 has been demonstrated to be of significance in EndMT in the diabetic heart (9). We also have demonstrated that p300 is upregulated in the cardiac tissues of diabetic animals (10). p300-Mediated histone acetylation is a key mechanism in regulating gene transcription.…”

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confidence: 80%

miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy

et al. 2015

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Hyperglycemia-induced endothelial injury is a key pathogenetic factor in diabetic cardiomyopathy. Endothelial injury may lead to a phenotypic change (i.e., endothelial-to-mesenchymal transition [EndMT]), causing cardiac fibrosis. Epigenetic mechanisms, through specific microRNA, may regulate such a process. We investigated the mechanisms for such changes in cardiac microvascular endothelial cells and in the heart of genetically engineered mice with chemically induced diabetes. Cardiac tissues and isolated mouse heart endothelial cells (MHECs) from animals with or without endothelial-specific overexpression of miR-200b, with or without streptozotocin-induced diabetes, were examined at the mRNA and protein levels for endothelial and mesenchymal markers. Expression of miR-200b and its targets was quantified. Cardiac functions and structures were analyzed. In the hearts of wild-type diabetic mice, EndMT was observed, which was prevented in the miR-200b transgenic diabetic mice. Expression of specific markers such as vascular endothelial growth factor, zinc finger E-box–binding homeobox, transforming growth factor-β1, and p300 were increased in the hearts of diabetic mice and were prevented following miR-200b overexpression. MHECs showed similar changes. miR-200b overexpression also prevented diabetes-induced cardiac functional and structural changes. These data indicate that glucose-induced EndMT in vivo and in vitro in the hearts of diabetic mice is possibly mediated by miR-200b and p300.

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confidence: 80%

miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy

et al. 2015

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“…7). The transcriptional co-activator p300 also functions as a HAT for H3/H4 and has been shown to interact with other E-box-binding proteins (21, 24 -27) and to be involved in the regulation of glucose-regulated genes (21)(22)(23). Its interaction with ChREBP may therefore not only explain how ChREBP induces H4 acetylation and recruitment of Pol II to the txnip promoter but may also be key for the molecular understanding of the regulation of other ChREBP target genes and their potential chromatin modification and transactivation.…”

Section: Discussionmentioning

confidence: 99%

“…The transcriptional co-activator and histone acetyltransferase (HAT) p300 has been shown to regulate the expression of other glucose-responsive genes, such as insulin and fibronectin (21)(22)(23), and to physically interact with other E-box-binding basic helix-loop-helix proteins, such as NeuroD (21), USF2 (24), MyoD (25), SREBP (26), and Myc (27). Moreover, p300 is one of the major HATs (in addition to HAT1 and TIP 60) that acetylate H4.…”

Section: The Txnip Promoter Contains a Putative Chrebp Binding Site-mentioning

confidence: 99%

Glucose-stimulated Expression of Txnip Is Mediated by Carbohydrate Response Element-binding Protein, p300, and Histone H4 Acetylation in Pancreatic Beta Cells

Cha-Molstad

Saxena

Chen

et al. 2009

Journal of Biological Chemistry

200

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Recently, we identified Txnip (thioredoxin-interacting protein) as a mediator of glucotoxic beta cell death and discovered that lack of Txnip protects against streptozotocin-and obesityinduced diabetes by preventing beta cell apoptosis and preserving endogenous beta cell mass. Txnip has therefore become an attractive target for diabetes therapy, but although we have found that txnip transcription is highly induced by glucose through a unique carbohydrate response element, the factors controlling this effect have remained unknown. Using transient transfection experiments, we now show that overexpression of the carbohydrate response element-binding protein (ChREBP) transactivates the txnip promoter, whereas ChREBP knockdown by small interfering RNA completely blunts glucose-induced txnip transcription. Moreover, chromatin immunoprecipitation demonstrated that glucose leads to a dose-and time-dependent recruitment of ChREBP to the txnip promoter in vivo in INS-1 beta cells as well as human islets. Furthermore, we found that the co-activator and histone acetyltransferase p300 co-immunoprecipitates with ChREBP and also binds to the txnip promoter in response to glucose. Interestingly, this is associated with specific acetylation of histone H4 and recruitment of RNA polymerase II as measured by chromatin immunoprecipitation. Thus, with this study we have identified ChREBP as the transcription factor that mediates glucose-induced txnip expression in human islets and INS-1 beta cells and have characterized the chromatin modification associated with glucose-induced txnip transcription. In addition, the results reveal for the first time that ChREBP interacts with p300. This may explain how ChREBP induces H4 acetylation and sheds new light on glucose-mediated regulation of chromatin structure and transcription.

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“…Remarkably, histone acetylation at inflammatory gene promoters in a CREB/ p300 (HAT)-dependent manner can be affected by oxidized lipids so that gene expression drives increased (36). In addition, PARP and NF-γB signaling was performed by p300 pathways in diabetic retina, kidney and heart, and led to extracellular matrix (ECM) components augmentation resulting in DVC (37)(38)(39)(40)(41)(42). Research in epigenetic showed that HDACs play a crucial role in TGF-β1-mediated ECM generation and renal parenchymal fibrosis (43)(44)(45).…”

Section: Histone Modificationmentioning

confidence: 99%

“…Furthermore, blood pressure control and fluid reabsorption are associated to dynamic regulation of H3K79 methylation (52)(53)(54)(55)(56). In addition, risk of diabetic complications increased as H3K4me and recruitment of SET7/9 to the insulin promoter region are augmented (38,56). Hyperglycemic memory may implicate epigenetic modifications through a transient hyperglycemia (57,58).…”

Section: Histone Modificationmentioning

confidence: 99%

Epigenetic Diabetic Vascular Complications

Ahmadzadeh-Amiri

2016

J Pediatr Rev

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Diabetic vascular complications (DVC) influence several vital organ systems including cardiovascular, renal, ocular and nervous systems making it a major public health problem. Although extensive researches were performed in this field, the exact mechanisms responsible for these organ damages in diabetes remain obscure. Several metabolic disturbances have been involved in its complication and change in genes associated with these pathways occurred. Gene expression to produce a biologically active protein can be controlled by transcriptional and translational alteration on the head of genes without change in nucleotide composition. These epigenetic adjustments are steady, but possibly reversible and can be transmitted to future generation. Gene expression can be regulated by three epigenetic mechanisms including DNA methylation, histone modifications and noncoding microRNAs (miRNAs) activity. Epigenetic studies must be directed to better realize the role of epigenetic changes to the etiology of DVC and knowledge of epigenetic would play a pivotal role in the application of individualized medicine. Application and development of high technology sequencing combined with more sensitive and advanced methodologies for epigenome studying help to determine specific epigenetic events that stimulate gene responses in patients with diabetes mellitus.

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Diabetes-Induced Extracellular Matrix Protein Expression Is Mediated by Transcription Coactivator p300

Cited by 93 publications

References 33 publications

miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy

miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy

Glucose-stimulated Expression of Txnip Is Mediated by Carbohydrate Response Element-binding Protein, p300, and Histone H4 Acetylation in Pancreatic Beta Cells

Epigenetic Diabetic Vascular Complications

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