Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

González-Ramos, Marta; Mora, Inés; Garcı́a, Soledad; Garesse, Rafael; Rodrı́guez-Puyol, Manuel; Olmos, Gemma; Rodríguez‐Puyol, Diego

doi:10.1016/j.biocel.2012.03.003

Cited by 23 publications

(12 citation statements)

References 51 publications

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“…[57][58][59][60] In addition, the EGF promoter has at least 13 AP1 sites in its promoter 61 and TGF-b2 is also promoted by AP1. 62 After activation of EGFR signaling pathways, ras and raf are activated resulting in phosphorylation of c-fos and c-jun and in an increased AP-1 activity. 57,[63][64][65] This increase in AP-1 activity leads to transcription of genes with AP-1 sites in their promoter 57,[63][64][65] Since the given growth factors all share AP-1 binding sites, they are potential targets for therapies that downregulate EGFR signaling pathways that result in reduced AP-1 activity.…”

Section: Discussionmentioning

confidence: 99%

EGFR-Blockade With Erlotinib Reduces EGF and TGF-β2 Expression and the Actin-Cytoskeleton Which Influences Different Aspects of Cellular Migration in Lens Epithelial cells

Wertheimer

Liegl

Kernt

et al. 2014

Current Eye Research

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Section: Discussionmentioning

confidence: 99%

EGFR-Blockade With Erlotinib Reduces EGF and TGF-β2 Expression and the Actin-Cytoskeleton Which Influences Different Aspects of Cellular Migration in Lens Epithelial cells

Wertheimer

Liegl

Kernt

et al. 2014

Current Eye Research

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“…Thus, pharmacological inhibition of different ROS sources, including NAD(P)H oxidase and the mitochondrial respiratory chain, decreases the transcription of Tgfb1 via reduced activity of activated protein 1 (24), indicating that ROS-induced enhancement of the transcription of Tgfb1 may at least in part account for the increase in Tgfb1 expression in diabetes. In vitro overexpression of Elmo1 in cultured COS cells increases the expression of Tgfb1 and its downstream extracellular matrix genes, including fibronectin, collagen 1A1 (5), and integrin-linked kinase (5).…”

Section: Discussionmentioning

confidence: 99%

High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

Hathaway

Chang

Grant

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2Akita gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.reactive oxygen species | 3′-untranslated region | fibrosis

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“…Indeed, there is clear evidence that ROS can stimulate the activation of the TGF-β pathway with important consequences on cellular functions (Fukawa et al, 2012, Gonzalez-Ramos et al, 2012), and it has also been demonstrated that this ROS-mediated regulation is dependent on c-Jun transcriptional activity (Gonzalez-Ramos et al, 2012). Furthermore, the established functions of CCM proteins in the regulation of both cadherin- and integrin-mediated cell adhesion and RhoA-dependent actin cytoskeleton dynamics might be directly related to the emerging important role of ROS and redox signaling in the modulation of the functional crosstalk between cadherins, integrins and small GTPases (Ferro et al, 2012, Goitre et al, 2012).…”

Section: Redox Signaling and Oxidative Stress: The Two Emerging Facesmentioning

confidence: 99%

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

Retta

Glading

2016

The International Journal of Biochemistry & Cell Biology

110

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Graphical abstractTowards a unifying mechanism for CCM disease pathogenesis and treatment.CCM proteins play pleiotropic roles in distinct redox-sensitive pathways by modulating the fine-tuned crosstalk between redox signaling and autophagy. Effective autophagy removes ROS-generating cellular trash, including damaged mitochondria, to rejuvenate cell environment, thus serving a cytoprotective function for the maintenance of endothelial cell monolayer integrity and functionality and blood–brain barrier (BBB) stability even under adverse stress conditions. Loss-of-function of a CCM protein (e.g., KRIT1) causes defective autophagy and altered redox signaling, affecting BBB stability and sensitizing endothelial cells to local oxidative stress and inflammatory events, which may act as key pathogenic determinants of focal formation and progression of CCM lesions. The common capacity to modulate the interplay between autophagy and redox signaling reconciles the distinct pharmacological approaches proposed so far for CCM disease prevention and treatment.

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Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

Cited by 23 publications

References 51 publications

EGFR-Blockade With Erlotinib Reduces EGF and TGF-β2 Expression and the Actin-Cytoskeleton Which Influences Different Aspects of Cellular Migration in Lens Epithelial cells

EGFR-Blockade With Erlotinib Reduces EGF and TGF-β2 Expression and the Actin-Cytoskeleton Which Influences Different Aspects of Cellular Migration in Lens Epithelial cells

High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

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