Disease Progression Mediated by Egr-1 Associated Signaling in Response to Oxidative Stress

Pagel, Judith-Irina; Deindl, Elisabeth

doi:10.3390/ijms131013104

Cited by 63 publications

(51 citation statements)

References 96 publications

(105 reference statements)

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“…The up-regulation of transcription factors known to be induced under oxidative stress was found in the less efficient, HRFI group. For example, the network integration analysis showed that EGR1 , known to induce “redox sensitive” genes27, interacts with several of the DE genes (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Gene expression differences in Longissimus muscle of Nelore steers genetically divergent for residual feed intake

Tizioto

Coutinho

Oliveira

et al. 2016

Sci Rep

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Residual feed intake (RFI), a measure of feed efficiency (FE), is defined as the difference between the observed and the predictable feed intake considering size and growth of the animal. It is extremely important to beef production systems due to its impact on the allocation of land areas to alternative agricultural production, animal methane emissions, food demand and cost of production. Global differential gene expression analysis between high and low RFI groups (HRFI and LRFI: less and more efficient, respectively) revealed 73 differentially expressed (DE) annotated genes in Longissimus thoracis (LT) muscle of Nelore steers. These genes are involved in the overrepresented pathways Metabolism of Xenobiotics by Cytochrome P450 and Butanoate and Tryptophan Metabolism. Among the DE transcripts were several proteins related to mitochondrial function and the metabolism of lipids. Our findings indicate that observed gene expression differences are primarily related to metabolic processes underlying oxidative stress. Genes involved in the metabolism of xenobiotics and antioxidant mechanisms were primarily down-regulated, while genes responsible for lipid oxidation and ketogenesis were up-regulated in HRFI group. By using LT muscle, this study reinforces our previous findings using liver tissue and reveals new genes and likely tissue-specific regulators playing key-roles in these processes.

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Section: Resultsmentioning

confidence: 99%

Gene expression differences in Longissimus muscle of Nelore steers genetically divergent for residual feed intake

Tizioto

Coutinho

Oliveira

et al. 2016

Sci Rep

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“…Egr-1 is a highly conserved, Cys 2 His 2 type zinc-finger transcription factor known to be induced by a variety of stimuli such as oxidative stress, shear stress, and growth factors, including PDGF (8,22,29,38). In patients with both congenital heart disease-associated PAH and idiopathic PAH, Egr-1 expression is abundant in plexiform lesions and in smooth muscle cells in vessels with severe concentric intimal fibrosis (51).…”

Section: Discussionmentioning

confidence: 99%

PDGF induces SphK1 expression via Egr-1 to promote pulmonary artery smooth muscle cell proliferation

Sysol

Natarajan

Machado

2016

American Journal of Physiology-Cell Physiology

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Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease for which there is currently no curative treatment available. Pathologic changes in this disease involve remodeling of the pulmonary vasculature, including marked proliferation of pulmonary artery smooth muscle cells (PASMCs). Recently, the bioactive lipid sphingosine-1-phosphate (S1P) and its activating kinase, sphingosine kinase 1 (SphK1), have been shown to be upregulated in PAH and promote PASMC proliferation. The mechanisms regulating the transcriptional upregulation of SphK1 in PASMCs are unknown. In this study, we investigated the role of platelet-derived growth factor (PDGF), a PAH-relevant stimuli associated with enhanced PASMC proliferation, on SphK1 expression regulation. In human PASMCs (hPASMCs), PDGF significantly increased SphK1 mRNA and protein expression and induced cell proliferation. Selective inhibition of SphK1 attenuated PDGF-induced hPASMC proliferation. In silico promoter analysis for SphK1 identified several binding sites for early growth response protein 1 (Egr-1), a PDGF-associated transcription factor. Luciferase assays demonstrated that PDGF activates the SphK1 promoter in hPASMCs, and truncation of the 5'-promoter reduced PDGF-induced SphK1 expression. Stimulation of hPASMCs with PDGF induced Egr-1 protein expression, and direct binding of Egr-1 to the SphK1 promoter was confirmed by chromatin immunoprecipitation analysis. Inhibition of ERK signaling prevented induction of Egr-1 by PDGF. Silencing of Egr-1 attenuated PDGF-induced SphK1 expression and hPASMC proliferation. These studies demonstrate that SphK1 is regulated by PDGF in hPASMCs via the transcription factor Egr-1, promoting cell proliferation. This novel mechanism of SphK1 regulation may be a therapeutic target in pulmonary vascular remodeling in PAH.

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“…Egr-1 is an inducible factor that does not occur in normal colonic mucosa, but it is activated by an oxidative stress. Egr-1 can activate expression of many angiogenic factors (bFGF, PDGF-A, PDGF-B, VEGF, VEG-FR-1, angiopoentin-1, proteases), as well as pro-inflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-2, monocyte chemotactic protein-1, tissue factor, GM-CSF) by interaction with the proximal promoter region of gene or by protein-protein interaction with other transcription factors [7,14].…”

Section: Resultsmentioning

confidence: 99%

The disturbance of oxidant-antioxidant balance in rat colonic mucosa after antibiotic therapy

Holota¹,

Tjapko²,

Dovbynchuk³

et al. 2015

Biol. Stud.

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Antibiotic treatment increases susceptibility to development of inflammatory bowel diseases (IBD) both in children and adults. Oxidative stress plays a prominent role in IBD pathogenesis. The aim of present study was to test an interrelationship between the morphological changes in rat colonic mucosa, the levels of antioxidant enzymes and redox sensitive transcription factors Egr-1 and Sp-1 after treatment with cephalosporin antibiotic ceftriaxone (Cf) with broad spectrum of action. Study was performed on male Wistar rats (180-230 g). Cf (50 mg/kg, i.m.) were injected daily for 5 days. The colonic levels of catalase and superoxide dismutase activity were measured by the colorimetric assays and zymography; levels of Egr-1 and Sp-1 -by Western-blot analysis; histological chan ges -by morphometric analysis. Body weight and diarrhea were recorded. Systemic administration of the ceftriaxone induced morphological and functional changes in rat colonic mucosa associated with initial stages of the acute inflammation. These changes were accompanied by a decrease of activity of superoxide dismutase and catalase. Levels of redox-sensitive transcription factors Egr-1 and Sp1 were significantly increased, which shows a disturbance of homeostasis of the intestinal barrier.

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Disease Progression Mediated by Egr-1 Associated Signaling in Response to Oxidative Stress

Cited by 63 publications

References 96 publications

Gene expression differences in Longissimus muscle of Nelore steers genetically divergent for residual feed intake

Gene expression differences in Longissimus muscle of Nelore steers genetically divergent for residual feed intake

PDGF induces SphK1 expression via Egr-1 to promote pulmonary artery smooth muscle cell proliferation

The disturbance of oxidant-antioxidant balance in rat colonic mucosa after antibiotic therapy

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