Reactive oxygen species and Wnt signalling crosstalk patterns mouse extraembryonic endoderm

Wen, Jason; Hwang, Juliana; Kelly, Gregory M.

doi:10.1016/j.cellsig.2012.07.024

Cited by 23 publications

(33 citation statements)

References 58 publications

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“…b-Catenin abundance asymmetrically followed WIF-1 suppression: low WIF-1 expression correlated with high total and nuclear b-catenin accumulation, leading to increased Wnt signaling, as seen in colon cells (38) or in mouse ectoderm (39). ROS can activate ATM directly (20,40) or through DNA damage (22), but we also propose that ROS are induced by the activity of ATM because inhibition of ATM reduced ROS.…”

Section: Wif-1 Is a Ros Markermentioning

confidence: 72%

Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis

et al. 2014

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Systemic sclerosis (SSc) is an autoimmune disease characterized by extensive visceral organ and skin fibrosis. SSc patients have increased production of autoreactive antibodies and Wnt signaling activity. We found that expression of the gene encoding Wnt inhibitor factor 1 (WIF-1) was decreased in fibroblasts from SSc patient biopsies. WIF-1 deficiency in SSc patient cells correlated with increased abundance of the Wnt effector β-catenin and the production of collagen. Knocking down WIF-1 in normal fibroblasts increased Wnt signaling and collagen production. WIF-1 loss and DNA damage were induced in normal fibroblasts by either SSc patient immunoglobulins or oxidative DNA-damaging agents, such as ultraviolet light, hydrogen peroxide, or bleomycin. The DNA damage checkpoint kinase ataxia telangiectasia mutated (ATM) mediated WIF-1 silencing through the phosphorylation of the transcription factor c-Jun, which in turn activated the expression of the gene encoding activating transcription factor 3 (ATF3). ATF3 and c-Jun were recruited together with histone deacetylase 3 (HDAC3) to the WIF-1 promoter and inhibited WIF-1 expression. Preventing the accumulation of reactive oxygen species or inhibiting the activation of ATM, c-Jun, or HDACs restored WIF-1 expression in cultured SSc patient cells. Trichostatin A, an HDAC inhibitor, prevented WIF-1 loss, β-catenin induction, and collagen accumulation in an experimental fibrosis model. Our findings suggest that oxidative DNA damage induced by SSc autoreactive antibodies enables Wnt activation that contributes to fibrosis.

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Section: Wif-1 Is a Ros Markermentioning

confidence: 72%

Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis

et al. 2014

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“…It should be mentioned that although inactivation of Sec was sufficient to inhibit Wnt activity, we cannot exclude the possibility that GPX4 and Gpx4b might partially affect Wnt signaling indirectly. For example, depletion of GPX4 leads to increased cellular ROS, which activates multiple signaling pathways, including Wnt/β-catenin signaling (Funato et al, 2006(Funato et al, , 2010Kajla et al, 2012;Love et al, 2013;Rharass et al, 2014;Sandieson et al, 2014;Wen et al, 2012). Future studies are needed to elucidate such additional mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Glutathione peroxidase 4 inhibits Wnt/β-catenin signaling and regulates dorsal organizer formation in zebrafish embryos

et al. 2017

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The Wnt/β-catenin signaling pathway plays pivotal roles in axis formation during embryogenesis and in adult tissue homeostasis. Glutathione peroxidase 4 (GPX4) is a selenoenzyme and participates in the reduction of peroxides. Its synthesis depends on the availability of the element selenium. However, the roles of GPX4 in vertebrate embryonic development and underlying mechanisms are largely unknown. Here, we show that maternal loss of zebrafish gpx4b promotes embryonic dorsal organizer formation, whereas overexpression of gpx4b inhibits the development of the dorsal organizer. Depletion of human GPX4 and zebrafish gpx4b (GPX4/ gpx4b) increases, while GPX4/gpx4b overexpression decreases, Wnt/β-catenin signaling in vivo and in vitro. Functional and epistatic studies showed that GPX4 functions at the Tcf/Lef level, independently of selenocysteine activation. Mechanistically, GPX4 interacts with Tcf/Lefs and inhibits Wnt activity by preventing the binding of Tcf/Lefs to the promoters of Wnt target genes, resulting in inhibitory action in the presence of Wnt/β-catenin signaling. Our findings unravel GPX4 as a suppressor of Wnt/β-catenin signals, suggesting a possible relationship between the Wnt/β-catenin pathway and selenium via the association of Tcf/Lef family proteins with GPX4.

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“…In the second step, four signaling pathways (ARE, GR, Wnt, and NFAT) were identified as the potential mediator for the initial action of ebselen by analyzing gene promoters of the four key regulators of GSIS. Indeed, these pathways are highly responsive to redox regulation (31,32,62,70) and involved in transcriptional regulation of the key regulators of GSIS (8,24,59,65). In the third step, the candidate pathways (ARE and GR) and mediators (PGC-1a and C/EBPb) were chosen based on their gene expression responsiveness to ebselen.…”

Section: Figmentioning

confidence: 99%

“…Polymorphisms of gr are associated with type 2 diabetes with low insulin levels and attenuated first phase of GSIS in women (65). The third is the wingless-type MMTV integration site (Wnt) pathway that is positively regulated by ROS or H 2 O 2 (70). Elevated oxidation status by selenium (Se) deficiency (33) or GPX3 knockout (4) activated the Wnt pathway in mice.…”

Section: Introductionmentioning

confidence: 99%

Glutathione Peroxidase Mimic Ebselen Improves Glucose-Stimulated Insulin Secretion in Murine Islets

Wang

Yun²,

Lei³

2014

Antioxidants & Redox Signaling

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Aims: Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. Results: Ebselen improved GSIS in islets of all four tested genotypes. The rescue in the GPX1 knockout resulted from a coordinated transcriptional regulation of four key GSIS regulators and was mediated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a)-mediated signaling pathways. In contrast, CuDIPs improved GSIS only in the SOD1 knockout and suppressed gene expression of the PGC-1a pathway. Innovation: Islets from the GPX1 and(or) SOD1 knockout mice provided metabolically controlled intracellular hydrogen peroxide (H 2 O 2 ) and superoxide conditions for the present study to avoid confounding effects. Bioinformatics analyses of gene promoters and expression profiles guided the search for upstream signaling pathways to link the ebselen-initiated H 2 O 2 scavenging to downstream key events of GSIS. The RNA interference was applied to prove PGC-1a as the main mediator for that link. Conclusion: Our study revealed a novel metabolic use and clinical potential of ebselen in rescuing GSIS in the GPX1-deficient islets and mice, along with distinct differences between the GPX and SOD mimics in this regard. These findings highlight the necessities and opportunities of discretional applications of various antioxidant enzyme mimics in treating insulin secretion disorders. Redox Signal. 20,[191][192][193][194][195][196][197][198][199][200][201][202][203]

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Reactive oxygen species and Wnt signalling crosstalk patterns mouse extraembryonic endoderm

Cited by 23 publications

References 58 publications

Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis

Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis

Glutathione peroxidase 4 inhibits Wnt/β-catenin signaling and regulates dorsal organizer formation in zebrafish embryos

Glutathione Peroxidase Mimic Ebselen Improves Glucose-Stimulated Insulin Secretion in Murine Islets

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