Loss of EGR-1 uncouples compensatory responses of pancreatic β cells

Leu, Sy-Ying; Kuo, Li-Chieh; Weng, Wen-Tsan; Lien, I-Chia; Yang, Ching-Chun; Hsieh, Tai-Tzu; Cheng, Yi-Ning; Chien, Po‐Hsiu; Ho, L.T.; Chen, Shun Hua; Shan, Yan-Shen; Chen, Yun-Wen; Chen, Pei–Chun; Tsai, Pei-Jane; Sung, Junne-Ming; Tsai, Yau‐Sheng

doi:10.7150/thno.40664

Cited by 11 publications

(10 citation statements)

References 46 publications

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“…Penrod et al [ 87 ] proved that the reduction of Arc produced significant deficits in both object and social novelty preference tasks what is also in line with our observations and it pointed out that the induction of Arc is necessary for normal novelty behavior suggesting inter alia this gene as a regulator of detection of novelty [ 87 ]. In addition, recent study proved that mice deficient in EGR-1 ( Egr1 −/− ) fed with high-fat diet failed to secrete sufficient insulin to clear glucose, which was associated with lower insulin content and the development of pancreatic islet failure [ 90 ]. It is known that early growth response gene 1 ( Egr1 ) is implicated in the regulation of cell differentiation, proliferation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that early growth response gene 1 ( Egr1 ) is implicated in the regulation of cell differentiation, proliferation, and apoptosis. The deficiency of EGR-1 might influence β-cell compensation in response to metabolic overload what [ 90 ]. These findings highlight the importance of this gene in the future studies focused on diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…Cytokine concentrations in prefrontal cortex were expressed in picograms per mg protein. Protein concentration was determined according to the method of Bradford [ 90 ].…”

Section: Methodsmentioning

confidence: 99%

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The Role of Molecular and Inflammatory Indicators in the Assessment of Cognitive Dysfunction in a Mouse Model of Diabetes

Piątkowska‐Chmiel

Herbet

Gawrońska‐Grzywacz

et al. 2021

IJMS

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The brain is the most vulnerable organ to glucose fluctuations, as well as inflammation. Considering that cognitive impairment might occur at the early stage of diabetes, it is very important to identify key markers of early neuronal dysfunction. Our overall goal was to identify neuroinflammatory and molecular indicators of early cognitive impairment in diabetic mice. To confirm cognitive impairment in diabetic mice, series of behavioral tests were conducted. The markers related to cognitive decline were classified into the following two groups: Neuroinflammatory markers: IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and genetic markers (Bdnf, Arc, Egr1) which were estimated in brain regions. Our studies showed a strong association between hyperglycemia, hyperinsulinemia, neuroinflammation, and cognitive dysfunction in T2DM mice model. Cognitive impairment recorded in diabetes mice were associated not only with increased levels of cytokines but also decreased Arc and Egr1 mRNA expression level in brain regions associated with learning process and memory formation. The results of our research show that these indicators may be useful to test new forms of treatment of early cognitive dysfunction associated not only with diabetes but other diseases manifesting this type of disorders. The significant changes in Arc and Egr1 gene expression in early stage diabetes create opportunities it possible to use them to track the progression of CNS dysfunction and also to differential disease diagnosis running with cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Role of Molecular and Inflammatory Indicators in the Assessment of Cognitive Dysfunction in a Mouse Model of Diabetes

Piątkowska‐Chmiel

Herbet

Gawrońska‐Grzywacz

et al. 2021

IJMS

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“…It has recently been reported that EGR-1 plays a crucial role in promoting β cell identity, maintaining β cell characteristics, and repressing non-β cell programs [ 19 ]. Moreover, EGR-1 is known to contribute to the glucose responsiveness and function of pancreatic β cells through the regulation of insulin and Pdx1 expression [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, EGR-1 has recently been reported as a critical factor to promote β cell identity, maintain β cell characteristics, and repress non-β cell programs [ 19 ]. This study describes how the loss of EGR-1 uncouples metabolic stress from the transcriptional cascade essential for the β cell compensatory response, which underscores EGR-1 as a critical factor in the pathogenesis of pancreatic islet failure.…”

Section: Introductionmentioning

confidence: 99%

Pdx1 Is Transcriptionally Regulated by EGR-1 during Nitric Oxide-Induced Endoderm Differentiation of Mouse Embryonic Stem Cells

Salguero-Aranda

Beltrán-Povea

Postigo-Corrales

et al. 2022

IJMS

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The transcription factor, early growth response-1 (EGR-1), is involved in the regulation of cell differentiation, proliferation, and apoptosis in response to different stimuli. EGR-1 is described to be involved in pancreatic endoderm differentiation, but the regulatory mechanisms controlling its action are not fully elucidated. Our previous investigation reported that exposure of mouse embryonic stem cells (mESCs) to the chemical nitric oxide (NO) donor diethylenetriamine nitric oxide adduct (DETA-NO) induces the expression of early differentiation genes such as pancreatic and duodenal homeobox 1 (Pdx1). We have also evidenced that Pdx1 expression is associated with the release of polycomb repressive complex 2 (PRC2) and P300 from the Pdx1 promoter; these events were accompanied by epigenetic changes to histones and site-specific changes in the DNA methylation. Here, we investigate the role of EGR-1 on Pdx1 regulation in mESCs. This study reveals that EGR-1 plays a negative role in Pdx1 expression and shows that the binding capacity of EGR-1 to the Pdx1 promoter depends on the methylation level of its DNA binding site and its acetylation state. These results suggest that targeting EGR-1 at early differentiation stages might be relevant for directing pluripotent cells into Pdx1-dependent cell lineages.

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Pancreatic islet cell type–specific transcriptomic changes during pregnancy and postpartum

Chung¹,

Ma²,

Zhang³

et al. 2023

iScience

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Loss of EGR-1 uncouples compensatory responses of pancreatic β cells

Cited by 11 publications

References 46 publications

The Role of Molecular and Inflammatory Indicators in the Assessment of Cognitive Dysfunction in a Mouse Model of Diabetes

The Role of Molecular and Inflammatory Indicators in the Assessment of Cognitive Dysfunction in a Mouse Model of Diabetes

Pdx1 Is Transcriptionally Regulated by EGR-1 during Nitric Oxide-Induced Endoderm Differentiation of Mouse Embryonic Stem Cells

Pancreatic islet cell type–specific transcriptomic changes during pregnancy and postpartum

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