• Molecules and Cells
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• v.40 no.1
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• pp.45-53
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• 2017

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

• BMB Reports
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• v.41 no.7
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• pp.485-494
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• 2008

The Wnt signaling network, which is composed of Wnt ligands, receptors, antagonists, and intracellular signaling molecules, has emerged as a powerful regulator of cell fate, proliferation, and function in multicellular organisms. Over the past two decades, the critical role of Wnt signaling in embryonic cartilage and bone development has been well established, and much has been learnt regarding the role of Wnt signaling in chondrogenesis and cartilage development. However, relatively little is known about the role of Wnt signaling in adult articular cartilage and degenerative cartilage tissue. This review will briefly summarize recent advances in Wnt regulation of chondrogenesis and hypertrophic maturation of chondrocytes, and review data concerning the role of Wnt signaling in the maintenance and degeneration of articular chondrocytes and cartilage.

• Journal of Life Science
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• v.19 no.10
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• pp.1346-1351
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• 2009

Recent evidence has shown that many pluripotetic neural crest cells are fate-restricted and that different fate-restricted crest cells emigrate from the neural tube at different times. Jin et al. (2001) identified the expression patterns of Wnts and its antagonists at the time that neural crest cells were being specified and suggested that Wnt signaling was involved in the segregation/differentiation of neural crest cells in the trunk in vitro. In this study, we evaluated the effects of Wnt signaling in avian neural crest lineage segregation. To accomplish this, Wnt signaling was disturbed at the time of neural crest segregation and differentiation by grafting Wnt-3a expressing cells and conducting dominant negative glycogen synthase kinase (dnGSK) electroporation. Stimulation of Wnt signaling induced neural crest lineage segregation and melanoblast specification, and increased the expression levels of genes known to be involved in neural crest development such as cadherin 7 and Slug, which suggests that they are involved in Wnt-induced neural crest lineage differentiation into melanoblasts.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.413-421
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• 2014

Corticotropin-releasing factor (CRF) is involved in the stress response and there is increasing evidence that stress influences skin disease such as hair loss. In cultured human hair follicles, CRF inhibits hair shaft elongation, induces premature regression and promotes the apoptosis of hair matrix keratinocytes. We investigated whether CRF influences the dermal papilla cells (DPC) that play pivotal roles in hair growth and cycling. Human DPCs were treated with CRF, adrenocorticotropic hormone (ACTH) and cortisol, key stress hormones along the hypothalamic-pituitary -adrenal (HPA) axis for 1-24 h. Interestingly, CRF modulated the expression of cytokines related to hair growth (KGF, Wnt5a, $TGF{\beta}-2$, Nexin) and increased cAMP production in cultured DPCs. CRF receptors were down-regulated by negative feedback systems. Pretreatment of CRF receptor antagonists or protein kinase A (PKA) inhibitor prevented the CRF-induced modulation. Since the CRF induces proopiomelanocortin (POMC) expression through the cAMP/PKA pathway, we analyzed POMC mRNA. CRF stimulated POMC expression in cultured human DPCs, yet we were unable to detect ACTH levels by western blot. These results indicate that CRF operates within DPCs through CRF receptors along the classical CRF signaling pathway and CRF receptor antagonists could serve as potential therapeutic and cosmetic agents for stress-induced hair loss.