Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis

Lyros, Orestis; Rafiee, Parvaneh; Nie, Lei; Medda, Rituparna; Jovanović, Nebojša; Schmidt, Jamie; Mackinnon, Alexander C.; Venu, Nanda; Shaker, Reza

doi:10.1152/ajpgi.00153.2013

Cited by 28 publications

(25 citation statements)

References 51 publications

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“…We found that while DKK1 cooperates with ZEB1 in the repression of H2AFY , repression of CDKN2A and CDKN2B by ZEB1 is independent of DKK1 levels. Evidence in the extant literature for a role of DKK1 in senescence is inconclusive as DKK1 expression decreases in senescent endothelial cells but DKK1 mediates senescence in oesophagous epithelial cells,54 55 indicating once again that DKK1, as other Wnt antagonists, plays opposing functions under different physiological and pathological contexts. In contrast to DKK1, DKK3 failed to induce the mutant p53-Mdm2-CtBP pathway or to inhibit senescence in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

ZEB1-induced tumourigenesis requires senescence inhibition via activation of DKK1/mutant p53/Mdm2/CtBP and repression of macroH2A1

Barrios

Győrffy

Fernández-Aceñero

et al. 2016

Gut

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Section: Discussionmentioning

confidence: 99%

ZEB1-induced tumourigenesis requires senescence inhibition via activation of DKK1/mutant p53/Mdm2/CtBP and repression of macroH2A1

Barrios

Győrffy

Fernández-Aceñero

et al. 2016

Gut

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“…The other gene upregulated in the WAG/OXYS-1.1 strain is the Dkk1 gene, the product of which influences eye development from a defined developmental time point on, and is essential for lens separation from the surface ectoderm [ 96 ]. The function of Dkk1 has not been analyzed in detail in terms of eye development, but most likely the resulting protein acts in a dose-dependent manner, as a competent antagonist of canonical Wnt signaling [ 97 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

et al. 2014

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BackgroundEtiology of complex disorders, such as cataract and neurodegenerative diseases including age-related macular degeneration (AMD), remains poorly understood due to the paucity of animal models, fully replicating the human disease. Previously, two quantitative trait loci (QTLs) associated with early cataract, AMD-like retinopathy, and some behavioral aberrations in senescence-accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and WAG rats. To confirm the findings, we generated interval-specific congenic strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome 1 in the WAG strain. Both congenic strains displayed early cataract and retinopathy but differed clinically from OXYS rats. Here we applied a high-throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the candidate genes and functional pathways that may be responsible for these differences and can contribute to the development of the senescence-accelerated phenotype of OXYS rats.ResultsFirst, the size and map position of QTL-derived congenic segments were determined by comparative analysis of coding single-nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and congenic retinal RNAs after sequencing. The transferred locus was not what we expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed. Coherent sets of differentially expressed genes were identified when we compared RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats. The genes most different in the average expression level between the congenic strains included those generally associated with the Wnt, integrin, and TGF-β signaling pathways, widely involved in neurodegenerative processes. Several candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs, Car9 and Fn1) were found to be either polymorphic in the congenic loci or differentially expressed between the strains. These genes may contribute to the development of cataract and retinopathy.ConclusionsThis study is the first RNA-Seq analysis of the rat retinal transcriptome generated with 40 mln sequencing read depth. The integration of QTL and transcriptomic analyses in our study forms the basis of future research into the relationship between the candidate genes within the congenic regions and specific changes in the retinal transcriptome as possible causal mechanisms that underlie age-associated disorders.

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“…β-catenin is primarily located in various cell membranes and in the cytoplasm. The β-catenin located in cell membranes mediates cell adhesion; the β-catenin in the cytoplasm is involved in the expression of genes, leading to cell proliferation, differentiation and apoptosis [16] In the process of embryonic development, most downstream target genes of the Wnt/β-catenin signaling pathway are important genes involved in cell cycle regulation, i.e., regulating generation, growth and development [17] The continuous activation of the Wnt/β-catenin signaling pathway in the Sertoli cells of post-natal mice could result in infertility in male mice, which is manifestedas degenerated seminiferous tubules, loss of spermatogenic cells, suppressed maturation of Sertoli cells and proliferation of Sertoli cells after adulthood [18] However, the inactivation of the β-catenin gene (CTNNB1) could also lead to partial infertility, reduced sperm count and abnormal spermatogenesis [8] Thus, the expression and level of β-catenin play important roles in the generation of sperm.…”

Section: Discussionmentioning

confidence: 99%

Development of Testes and Expression of Beta-catenin in Testes Tissue of Mice Born from Vitrified/Cryopreserved Embryos

Liang¹,

Wang²,

Hu³

et al. 2017

JFIV Reprod Med Genet

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Objective: To evaluate the impact of vitrifying embryo from mice on the development of testes of offspring. Materials and methods:This study included 60 male offspring mice, 30 male mice from transferred vitrified embryos and 30 male mice from transferred fresh embryos. We tested the morphology and β-catenin gene expression of testes of difference time after they born. Results:The HE staining results of the testes of the vitrification group and the fresh group showed dark blue staining in the nuclei and varying degrees of red staining in the cytoplasm and fibrous tissue. And there were no significant differences in the morphology of the testis tissues at the different developmental stages between the two groups. With the use of reverse transcription polymerase chain reaction and Western blotting, the data showed that there were no significant differences in the expression of β-catenin in the testes between the two groups of mice at different developmental stages. Conclusion:These data suggest that vitrifying pre-implantation embryos may have no effects on morphology and β-catenin gene expression of the testes of offspring.

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Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis

Abstract: Lyros O, Rafiee P, Nie L, Medda R, Jovanovic N, Schmidt J, Mackinnon A, Venu N, Shaker R. Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.

Cited by 28 publications

References 51 publications

ZEB1-induced tumourigenesis requires senescence inhibition via activation of DKK1/mutant p53/Mdm2/CtBP and repression of macroH2A1

ZEB1-induced tumourigenesis requires senescence inhibition via activation of DKK1/mutant p53/Mdm2/CtBP and repression of macroH2A1

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

Development of Testes and Expression of Beta-catenin in Testes Tissue of Mice Born from Vitrified/Cryopreserved Embryos

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