Histone Deacetylase Inhibitors Modulate the Transcriptional Regulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene

Kumar, Prerna; Tripathi, Satyabha; Pandey, Kailash N.

doi:10.1074/jbc.m113.511444

Cited by 39 publications

(31 citation statements)

References 63 publications

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“…Indeed, both HNF4a and SP1, besides transcriptional activation, also have been shown to function as transcriptional repressors in a cell type, stimulus, and gene-specific manner. 35,46,47 Taken together, the data indicate that in hepatocytes ethanol treatment can influence the function of HNF4a and SP1, leading to a transition from transcriptional activators to repressors that underlie ethanol-induced down-regulation of CPT-1A gene expression.…”

Section: Discussionmentioning

confidence: 77%

Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury

Donde

Ghare

Joshi‐Barve

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 77%

Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury

Donde

Ghare

Joshi‐Barve

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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“…Promoter region of the GC-A gene contains three potential Sp1-binding sites and their involvement in gene activation has been demonstrated (Liang et al, 1999;Garg et al, 2002). A few reports have shown that the Sp1 protein is involved in activation of the GC-A gene (Liang et al, 2001;Kumar et al, 2014). However, mechanisms of Sp1-mediated activation of the GC-A gene in different cell types remain unresolved.…”

Section: Discussionmentioning

confidence: 99%

Sp1 mediates phorbol ester (PMA)-induced expression of membrane-bound guanylyl cyclase GC-A in human monocytic cells*

et al. 2018

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Cyclic guanosine monophosphate (cGMP) is synthesized by two types of enzymes: particulate (membrane-bound) guanylyl cyclases (pGCs) and soluble (cytosolic) guanylyl cyclases (sGCs). sGCs are primarily activated by binding of nitric oxide to their prosthetic heme group while pGCs are activated by binding of peptide ligands to their extracellular domains. One of them, pGC type A (GC-A) is activated by atrial and brain natriuretic peptides (ANP and BNP, respectively). Human monocytes isolated from peripheral blood mononuclear cells have been found to display sGC expression without concomitant expression of GC-A. However, GC-A activity appears in monocytes under certain conditions but a molecular mechanism of GC-A expression is still poorly understood. In this report we show that phorbol ester (PMA) induces transcription of a gene encoding GC-A in human monocytic THP-1 cells. Moreover, we find that PMA-treated THP-1 cells raise cGMP content following treatment with ANP. Studies using pharmacological inhibitors of protein kinases suggest involvement of protein kinase C (PKC), mitogen extracellular kinases (MEK1/2), and extracellular signal-regulated kinases (ERK1/2) in PMA-induced expression of the GC-A encoding gene in THP-1 cells. Finally, we show that PMA stimulates binding of Sp1 transcription factor to GC-rich DNA sequences and mithramycin A (a selective Sp1 inhibitor) inhibits expression of the GC-A mRNA in PMA-treated THP-1 cells. Taken together, our findings suggest that the PMA-stimulated PKC and MEK/ERK signaling pathways induce Sp1-mediated transcription of the GC-A encoding gene in human monocytic THP-1 cells.

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“…Primary antibodies against δEF1 (catalog number sc‐10573), pSmad2/3 (Ser423/425; catalog number sc‐11769), H1 (catalog number sc‐10806), α‐SMA (catalog number Sc‐56499), COL1A2 (catalog number sc‐8788) and β‐actin (catalog number Sc‐47778 HRP) were purchased from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA). Primary antibody for NPRA was produced as previously described .…”

Section: Methodsmentioning

confidence: 99%

“…The 5′ flanking region (~ 500 bp upstream of the start codon) of the Npr1 gene (encoding GC‐A/NPRA) contains binding sites for several known transcription factors, and appears to play a critical role in functional regulation and expression of this gene . Previous studies from our laboratory and by others have focused on the regulation of Npr1 gene expression and function, however, the complete molecular machinery regulating its expression and function is yet to be established .…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor β1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A – role of δEF1

et al. 2016

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The objective of this study was to determine the role of transforming growth factor-beta 1 (TGF-β1) in transcriptional regulation and function of guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) and whether a cross-talk exists between these two hormonal systems in target cells. After treatments of primary cultured rat thoracic aortic vascular smooth muscle cells (RTASMCs) and mouse mesangial cells (MMCs) with TGF-β1, the Npr1 promoter construct embodying delta-crystallin enhancer binding factor 1 (δEF1) site showed 85% reduction in luciferase activity in a time- and dose-dependent manner. TGF-β1 also significantly attenuated luciferase activity of Npr1 promoter by 62% and decreased the ANP-mediated relaxation of mouse denuded aortic rings ex vivo. Treatment of cells with TGF-β1, stimulated the protein levels of δEF1 by 2.4- to 2.8-fold and also significantly enhanced the phosphorylation of Smad 2/3; however, markedly reduced Npr1 mRNA and receptor protein levels. Overexpression of δEF1 showed a reduction in Npr1 promoter activity by 75% while the deletion or site-directed mutagenesis of δEF1 sites in Npr1 promoter, eliminated the TGF-β1-mediated repression of Npr1 transcription. TGF-β1 significantly increased the expression of α-smooth muscle actin and collagen type 1 alpha 2 in RTASMCs, which were markedly attenuated by ANP in NPRA overexpressing cells. Together, the present results suggest that an antagonistic cascade exists between TGF-β1/Smad/δEF1 pathways and Npr1 expression and receptor signaling relevant to renal and vascular remodeling, which might be critical in the regulation of blood pressure and cardiovascular homeostasis.

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Histone Deacetylase Inhibitors Modulate the Transcriptional Regulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene

Cited by 39 publications

References 63 publications

Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury

Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury

Sp1 mediates phorbol ester (PMA)-induced expression of membrane-bound guanylyl cyclase GC-A in human monocytic cells*

Transforming growth factor β1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A – role of δEF1

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