The transcription factor NURR1 exerts concentration-dependent effects on target genes mediating distinct biological processes

Johnson, Magen M.

doi:10.3389/fnins.2011.00135

Cited by 37 publications

(53 citation statements)

References 68 publications

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“…Nurr1 is a nuclear receptor transcription factor belonging to the NR4A family of orphan nuclear receptors and functions as a constitutively active transcription factor. Gene expression profiling of cells overexpressing Nurr1 has shown that miR-217 is a target of Nurr1 (28). The D 2 R interacts with Nurr1 via ERK signaling and is critical for its transcription (29).…”

Section: Discussionmentioning

confidence: 99%

miR-217 Mediates the Protective Effects of the Dopamine D2 Receptor on Fibrosis in Human Renal Proximal Tubule Cells

et al. 2015

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Lack or downregulation of the dopamine D2 receptor (D2R) increases the vulnerability to renal inflammation independently of blood pressure in mice. Common single nucleotide polymorphisms (SNPs) rs 6276, 6277 and 1800497 in the human D2R gene are associated with decreased receptor expression/function, and hypertension. Human renal proximal tubule cells from subjects carrying these SNPs have decreased D2R expression and increased expression of pro-fibrotic factors and production of extracellular matrix proteins. We tested the hypothesis that the D2R mediates these effects by regulating microRNA expression. In cells carrying D2R SNPs, microRNAs (miRs)-217, -224, -335 and -1265 were downregulated while miR-1290 was upregulated more than 4-fold compared with those carrying D2R wild-type (WT) alleles. However, only miR-217 was directly regulated by D2R expression. In cells carrying D2R WT, miR-217 inhibitor increased the expression of TGFβ1, MMP3, FN1, and Col1a while miR-217 mimic had the opposite effect. In cells carrying D2R SNPs, miR-217 mimic also decreased the expression of TGFβ1 and its targets. Wnt5a, a miR-217 target, was increased in cells carrying D2R SNPs, and decreased by miR-217 mimic but increased by miR-217 inhibitor in both cell types. In cells carrying D2R WT, Wnt5a treatment increased TGFβ1 while silencing Ror2, a Wnt5a receptor, decreased TGFβ1 and blunted the Wnt5a-induced increase in cells carrying D2R WT. Our results show that renal proximal tubule cells from subjects carrying D2R SNPs resulting in D2R downregulation have increased TGFβ1 that is mediated by decreased regulation of the miR-217-Wnt5a-Ror2 pathway.

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Section: Discussionmentioning

confidence: 99%

miR-217 Mediates the Protective Effects of the Dopamine D2 Receptor on Fibrosis in Human Renal Proximal Tubule Cells

et al. 2015

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“…Studies in human neural SK-N-AS cells were conducted in which a number of stable clonal lines were constructed with graded NR4A2 gene expression to approximate levels of NR4A2 seen in dopaminergic neurons present in human substantia nigra [147]. Transcriptomic data acquired from these NR4A2-expressing clonal lines revealed that the effects of NR4A2 on target genes varied considerably as a function of its concentration.…”

Section: Nr4a2 In Cellular Homeostasis and Diseasementioning

confidence: 99%

Nuclear receptor 4A (NR4A) family – orphans no more

Safe

Jin

Morpurgo

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

157

161

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The orphan nuclear receptors NR4A1, NR4A2 and NR4A3 are immediate early genes induced by multiple stressors, and the NR4A1 receptors play an important role in maintaining cellular homeostasis and disease. There is increasing evidence for the role of these receptors in metabolic, cardiovascular and neurological functions and also in inflammation and inflammatory diseases and in immune functions and cancer. Despite the similarities of NR4A1, NR4A2 and NR4A3 and their interactions with common cis-genomic elements, they exhibit unique activities and cell-/tissue-specific functions. Although endogenous ligands for NR4A receptors have not been identified, there is increasing evidence that structurally-diverse synthetic molecules can directly interact with the ligand binding domain of NR4A1 and act as agonists or antagonists, and ligands for NR4A2 and NR4A3 have also been identified. Since NR4A receptors are key factors in multiple diseases, there are opportunities for the future development of NR4A ligands for clinical applications in treating multiple health problems including metabolic, neurologic and cardiovascular diseases, other inflammatory conditions, and cancer.

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“…The Nr4a genes are immediate-early genes transcribed rapidly in response to external stimuli (Peña de Ortiz & Jamieson, 1996). Mature NR4A proteins are capable of both positively and negatively regulating the transcription of their downstream targets (Johnson, Michelhaugh, Bouhamdan, Schmidt, & Bannon, 2011), which include plasticity-related genes such as Bdnf1 and Fosl2 (Hawk et al, 2012; Volpicelli et al, 2007). …”

Section: Introductionmentioning

confidence: 99%

The NR4A orphan nuclear receptors mediate transcription-dependent hippocampal synaptic plasticity

Bridi

Abel

2013

Neurobiology of Learning and Memory

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Memory consolidation and long-term potentiation require activity-dependent gene transcription, coordinated by an array of transcription factors. Many members of the nuclear receptor superfamily of transcription factors are expressed in the hippocampus immediately after learning, including the Nr4a family of orphan receptors. These activity-dependent transcription factors are critical for hippocampus-dependent contextual fear and object recognition memory, but their role in hippocampal synaptic function is unknown. In this study, we hypothesized that Nr4a transcription factor function is also necessary for hippocampal long-term potentiation. We used a strain of mice expressing a dominant-negative Nr4a transgene. Hippocampal slices from Nr4aDN mutant mice exhibited impairments in transcription-dependent long-term potentiation and were not sensitive to LTP enhancement by the HDAC inhibitor TSA. These results demonstrate that NR4A transcription factor function mediates mechanisms of synaptic plasticity in the hippocampus.

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The transcription factor NURR1 exerts concentration-dependent effects on target genes mediating distinct biological processes

Cited by 37 publications

References 68 publications

miR-217 Mediates the Protective Effects of the Dopamine D2 Receptor on Fibrosis in Human Renal Proximal Tubule Cells

miR-217 Mediates the Protective Effects of the Dopamine D2 Receptor on Fibrosis in Human Renal Proximal Tubule Cells

Nuclear receptor 4A (NR4A) family – orphans no more

The NR4A orphan nuclear receptors mediate transcription-dependent hippocampal synaptic plasticity

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