• 한국동물학회:뉴스레터
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• 제18권1호
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• pp.16-25
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• 2001

Wnt signaling의 주요 분자인 $\beta$-catenin의 기능과 조절에 관한 연구, 특히 TCF family 단백질과 함께 작용하는 신호전달에 관한 연구가 최근에 활발히 진행되고 있다. $\beta$-catenin 단백질은 Drosophila나 Xenopus의 발생초기에 중요한 역할을 한다는 것이 알려져 있고 Wnt (Wingless) 단백질에 의하여 활성화되는 신호전달 과정에 관여한다고 알려져 있으므로, TCF 단백질들이 Wnt signalling pathway에 작용한다는 것을 의미한다. 즉, $\beta$-catenin/TCF complex는 발생초기의 세포의 운명을 결정하는 세포의 분화에 중요하리라 생각된다. 또한 $\beta$-catenin/TCF complex는 세포의 암화에도 중요하다는 것이 보고되었다. 정상세포의 경우, $\beta$-catenin은 APC 라는 tumor suppressor에 의하여 결합하고 단백질의 분해가 유도되어 핵 안의 TCF와 결합하지 못하는데, 암세포의 경우 APC가 결실되었거나 $\beta$-catenin의 양이 과도하게 발현되어 암세포화 되는 것으로 보인다. 즉, $\beta$-catenin은 일종의 oncogene으로 작용하는 단백질이며, 그 작용에 필수적인 전사인자가 TCF라는 것이다. 특히, 대장암세포에서 이 $\beta$-catenin/TCF complex에 의해 활성화되는 유전자로서 c-myc과 cyclin Dl 등이 있는 것으로 보아, $\beta$-catenin/TCF 단백질은 세포의 증식 및 사멸에 관여하는 단백질들의 발현을 조절하는 매우 중요한 인자라고 생각된다.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.3.1-3.14
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• 2018

Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. $WNT/{\beta}$-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to $WNT/{\beta}$-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ${\beta}$-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ${\beta}$-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower $WNT/{\beta}$-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. After ${\beta}$-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of $WNT/{\beta}$-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.211-219
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• 2021

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

• 공업화학
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• 제32권6호
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• pp.647-652
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• 2021

본 연구에서는 에탄올과 노말헥산을 이용하여 당목향 뿌리 추출물을 제조하고, 인체 모유두세포의 세포증식 및 모발성장 관련 신호전달에 미치는 영향을 평가하였다. 당목향 뿌리 추출물의 세포증식 효과는 MTT assay를 실시하였으며, ERK, Akt, Wnt/𝛽-catenin 신호 경로, 5𝛼-reductase의 발현을 western blot 분석을 통해 측정하였다. 당목향 뿌리 추출물은 인체 모유두세포의 증식을 유의하게 증가시켰고, 세포증식에 관여하는 ERK와 Akt의 인산화를 촉진하였으며, 당목향 뿌리 추출물에 의해 증가된 ERK, Akt 인산화 촉진과 세포증식은 MEK/ERK 억제제 PD98059와 PI3K/Akt 억제제 LY294002에 의해 유의하게 감소되었다. 또한 당목향 뿌리 추출물은 GSK-3𝛽 (Ser9)의 인산화를 통한 𝛽-catenin(Ser552, 675)의 인산화를 촉진함으로써 핵 내의 𝛽-catenin 축적을 유도하였고, 5𝛼-reductase type I, II의 활성을 억제하였다. 종합적으로 당목향 뿌리 추출물은 모유두세포의 ERK, Akt 경로의 활성화를 통해 세포의 증식을 유도하며, 𝛽-catenin 신호 경로 활성화 및 5𝛼-reductase 활성 억제를 통해 탈모 예방 및 모발 성장 효과를 나타냄으로써 헤어케어제품의 소재로 응용가능성이 있음을 시사한다.

• BMB Reports
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• 제49권3호
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• pp.179-184
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• 2016

Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3905-3909
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• 2012

Ovarian cancer is the fifth leading cause of cancer death in women aged 35 to 74 years. Although there are several popular hypothesis of ovarian cancer pathogenesis, the genetic mechanisms are far from being clear. Recently, systems biology approaches such as network-based methods have been successfully applied to elucidate the mechanisms of diseases. In this study, we constructed a crosstalk network among ovarian cancer related pathways by integrating protein-protein interactions and KEGG pathway information. Several significant pathways were identified to crosstalk with each other in ovarian cancer, such as the chemokine, Notch, Wnt and NOD-like receptor signaling pathways. Results from these studies will provide the groundwork for a combination therapy approach targeting multiple pathways which will likely be more effective than targeting one pathway alone.

• 생약학회지
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• 제52권1호
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• pp.34-40
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• 2021

Proliferation and maintain of dermal papilla during progression of hair-cycle are crucial to the duration of anagen and regulated by diverse signaling pathway such as PI3K/Akt/Wnt/β-catenin pathway. In this study, we investigated the effects and mechanisms of Viola verecunda on dermal papilla cells. Treatment of dermal papilla cells with whole plant extract of V. verecunda resulted in cell proliferation, which was accompanied by up-regulation of cyclin D1, phospho (ser780)-pRB and cdc2 p34, and down-regulation of p27kip1. V. verecunda extract also promoted the levels of phospho (ser473)-Akt and phospho (ser780)-pRB in a time-dependent manner. Inhibition of PI3K/Akt by Wortmannin suppressed progression of cell-cycle, thereby attenuated the increases in proliferation of dermal papilla cells by V. verecunda extract. We further investigated Wnt/β-catenin pathway with respect to the effects of V. verecunda extract on the proliferation of dermal papilla cells. Treatment with V. verecunda extract results in up-regulation of Wnt/β-catenin proteins such as phospho (ser9)-GSKβ, phospho (ser552)-β-catenin and phospho (ser675)-β-catenin. In addition, Wortmannin abrogated V. verecunda extract mediated up-regulation of cdc2 p34 and down-regulation of p27kip1. These finding reveal that the proliferative effect of V. verecunda mediated by alteration of cell-cycle via activating PI3K/Akt/Wnt pathway in dermal papilla cells.

• BMB Reports
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• 제57권2호
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• pp.123-123
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• 2024

• Journal of Microbiology and Biotechnology
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• 제34권4호
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• pp.985-986
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• 2024