• YAKHAK HOEJI
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• v.56 no.6
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• pp.358-363
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• 2012

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine protein kinase, plays an important role in wide variety of developmental events. NLK phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional complex and suppresses wnt signaling pathway through inhibition of ${\beta}$-catenin/TCF complex interaction. However, the function of NLK in gastric carcinogenesis has not been investigated. In the present study, we have examined whether the NLK gene is involved in the development and/or progression of gastric cancers. NLK expression was analyzed by immunohistochemical staining in 153 advanced gastric cancer specimens. Immunhistochemical analysis showed increased expression of NLK in 91 (59.5%) out of 153 gastric cancer specimens. Statistically, there was no significant relationship between altered expression of NLK protein and clinicopathological parameters, including tumor differentiation, location, lymph node metastasis. We identified that mRNA and protein expression of NLK was significantly up-regulated in human gastric cancer tissues compare to corresponding normal gastric tissues. In addition, we found that human gastric cancer cell lines exhibited relatively high expression of NLK, as compared with normal gastric cells. The results of this study suggest that aberrant regulation of NLK may contribute to the development or progression of gastric cancers and serve as a potential biomarker for advanced gastric cancer patients.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.1-20
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• 2019

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, $Wnt/{\beta}-catenin$ and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.

• BMB Reports
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• v.55 no.12
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• pp.627-632
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• 2022

Dickkopf-1 (DKK1) is a secreted protein that acts as an antagonist of the canonical WNT/β-catenin pathway, which regulates osteoblast differentiation. However, the role of DKK1 on osteoblast differentiation has not yet been fully clarified. Here, we investigate the functional role of DKK1 on osteoblast differentiation. Primary osteoprogenitor cells were isolated from human spinal bone tissues. To examine the role of DKK1 in osteoblast differentiation, we manipulated the expression of DKK1, and the cells were differentiated into mature osteoblasts. DKK1 overexpression in osteoprogenitor cells promoted matrix mineralization of osteoblast differentiation but did not promote matrix maturation. DKK1 increased Ca⁺ influx and activation of the Ca⁺/calmodulin-dependent protein kinase II Alpha (CAMK2A)-cAMP response element-binding protein 1 (CREB1) and increased translocation of p-CREB1 into the nucleus. In contrast, stable DKK1 knockdown in human osteosarcoma cell line SaOS2 exhibited reduced nuclear translocation of p-CREB1 and matrix mineralization. Overall, we suggest that manipulating DKK1 regulates the matrix mineralization of osteoblasts by Ca⁺-CAMK2A-CREB1, and DKK1 is a crucial gene for bone mineralization of osteoblasts.

• Journal of Marine Bioscience and Biotechnology
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• v.15 no.1
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• pp.24-32
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• 2023

The Laminaria japonica Aresch (Sea tangle) belongs to the brown algae and has a long history as a food material in Asia, including Korea. Recent studies have found that the fermented Sea tangle extract (FST) inhibited the differentiation of osteoclasts and protected osteoblasts from oxidative damage. This study aims to explore the possibility that FST can induce the differentiation of osteoblasts and identify the responsible mechanism. According to our results, FST induced differentiation into osteogenic cells in the presence of osteoblastic MC3T3-E1 cells under non-toxic conditions.. This finding was confirmed by phalloidin staining, increased alkaline phosphatase activity, and calcium deposition. Additionally, it was found that this process was achieved by increasing the expression of key factors involved in osteoblast differentiation, such as runt-related transcription factor-2, osterix, β-catenin, and bone morphogenetic protein-2. Moreover, FST increased autophagy, which may contribute to the maintenance of the bone formation homeostasis, and is associated with the activation of the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways. Although further research about the bioactive substances contained in FST and the tests of their efficacy are required, the results of this study indicate that FST has incredible applicability as a functional material for maintaining the bone homeostasis.

• BMB Reports
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• v.56 no.7
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• pp.374-384
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• 2023

Fibrosis is a pathological condition that is characterized by an abnormal buildup of extracellular matrix (ECM) components, such as collagen, in tissues. This condition affects various organs of the body, including the liver and kidney. Early diagnosis and treatment of fibrosis are crucial, as it is a progressive and irreversible process in both organs. While there are certain similarities in the fibrosis process between the liver and kidney, there are also significant differences that must be identified to determine molecular diagnostic markers and potential therapeutic targets. Long non-coding RNAs (lncRNAs), a class of RNA molecules that do not code for proteins, are increasingly recognized as playing significant roles in gene expression regulation. Emerging evidence suggests that specific lncRNAs are involved in fibrosis development and progression by modulating signaling pathways, such as the TGF-β/Smad pathway and the β-catenin pathway. Thus, identifying the precise lncRNAs involved in fibrosis could lead to novel therapeutic approaches for fibrotic diseases. In this review, we summarize lncRNAs related to fibrosis in the liver and kidney, and propose their potential as therapeutic targets based on their functions.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.87-87
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• 2022

Under the COVID-19 pandemic, interest in immune enhancement and anti-obesity is increasing. Thus, in this study, we investigated whether Kadsura japonica fruits (KJF) exhibits immunostimulatory activity and anti-obesity activity. KJF increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. Inhibition of TLR2 and TLR4 blocked KJF-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of MAPK and PI3K/AKT signaling pathway reduced KJF-mediated production of immunostimulatory factors, and the activation of MAPK and PI3K/AKT signaling pathway by KJF suppressed the inhibition of TLR2/4. KJF attenuated the lipid accumulation and the protein expression such as CEBPα, PPARγ, perilipin-1, adiponectin, and FABP4 related to the lipid accumulation in 3T3-L1 cells. In addition, KJF inhibited excessive proliferation of 3T3-L1 cells and protein expressions such as β-catenin and cyclin D1 related to cell growth. These findings indicate that KJF may have immunostimulatory activity and anti-obesity activity.

• Korean Journal of Plant Resources
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• v.36 no.6
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• pp.541-548
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• 2023

In the present study, the effects of HML on lipolysis, adipocyte browning, autophagy, and proliferation were investigated. HML affected lipolysis by increasing the protein levels of ATGL and HSL, and phosphorylation levels of HSL and AMPK. Furthermore, HSL decreased the perilipin-1 levels. In addition, free glycerol content was increased by HML treatment. HML affected adipocyte browning by increasing the protein levels of UCP-1, PGC-1α, and PRDM16. In addition, HML affected autophagy by increasing the levels of LC3-I and LC3-II, and decreasing those of SQSTM1/p62. Moreover, HML affected adipocyte proliferation by suppressing the proliferation of 3T3-L1 cells due to arrest of the cell cycle via blocking the expression of β-catenin and cyclin D1. These results suggest that HML induces lipolysis, adipocyte browning, autophagy, and inhibits excessive proliferation of adipocytes.

• International Journal of Molecular Medicine
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• v.43 no.2
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• pp.1033-1040
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• 2019

Protein kinase casein kinase 2 (CK2) is important in the regulation of cell proliferation and death, even under pathological conditions. Previously, we reported that CK2 regulates the expression of heme oxygenase-1 (HO-1) in stress-induced chondrocytes. In the present study, it was shown that CK2 is involved in the dedifferentiation and cellular senescence of chondrocytes. Treatment of primary articular chondrocytes with CK2 inhibitors, 4,5,6,7-terabromo-2-azabenzimidazole (TBB) or 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB), induced an increase in senescence-associated β-galactosidase (SA-β-gal) staining. In addition, TBB reduced the expression of type II collagen and stimulated the accumulation of β-catenin, phenotypic markers of chondrocyte differentiation and dedifferentiation, respectively. It was also observed that the abrogation of CK2 activity by CK2 small interfering RNA induced phenotypes of chondrocyte senescence. The association between HO-1 and cellular senescence was also examined in CK2 inhibitor-treated chondrocytes. Pretreatment with 3-morpholinosydnonimine hydrochloride, an inducer of the HO-1 expression, or overexpression of the HO-1 gene significantly delayed chondrocyte senescence. These results show that CK2 is associated with chondrocyte differentiation and cellular senescence and that this is due to regulation of the expression of HO-1. Furthermore, the findings suggest that CK2 is crucial as an anti-aging factor during chondrocyte senescence.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.85-90
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• 2003

We investigated the effects of Oak smoke flavoring (OSF, Holyessing) on the growth of DU145 and PC-3 human prostate carcinoma cells. OSF treatment resulted in a concentration-dependent growth inhibition in both DU145 and PC3 cell lines. The anti-proliferative effect of OSF treatment was associated with the induction of apoptotic cell death which was confirmed by morphological change such as membrane shrinking, rounding up and chromatin condensation in DU145 and PC-3 cells. DNA flow cytometry analysis confirmed that OSF treatment increased population of apoptotic sub-G1 phase. Furthermore, we observed an increase of pro-apoptotic protein Bax expression and a decrease of anti-apoptotic protein Bcl-2 by OSF treatment in a dose-dependent manner. OSF also induced a proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase (PARP) and β-catenin proteins. The present results indicated that OSF-induced inhibition of human prostate carcinoma cell proliferation is associated with the induction of apoptosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.759-766
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• 2004

In the present study, we investigated the effects of aqueous extract of the healthful decoction utilizing Phellinus linteus (HDPL) on the cell growth of human lung carcinoma tumor cell line A549. Exposure of A549 cells to HDPL resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometric analysis. This increase in apoptosis was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase (PARP), b-catenin and phospholipase C- 1 (PLC- 1) protein. HDPL treatment induced the down-regulation of anti-apoptotic Bcl-2 expression, an anti-apoptotic gene, however, the level of Bax. a pro-apoptotic gene, was increased by HDPL treatment. In addition, HDPL-induced apoptotis of A549 cells was connected with activation of caspase-3 and caspase-9 protease in a dose-dependent manner, however, the levels of inhibitor of apoptosis proteins family were remained unchanged. Taken together, these results indicated that the anti-proliferative effects of HDPL were associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease activity, and HDPL may have therapeutic potential in human lung cancer.