• BMB Reports
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• v.53 no.8
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• pp.425-430
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• 2020

Tumor necrosis factor-inducible gene 6 protein (TSG-6) is a cytokine secreted by mesenchymal stem cells (MSCs) and regulates MSC stemness. We previously reported that TSG-6 changes primary human hepatic stellate cells (pHSCs) into stem-like cells by activating yes-associated protein-1 (YAP-1). However, the molecular mechanism behind the reprogramming action of TSG-6 in pHSCs remains unknown. Cluster of differentiation 44 (CD44) is a transmembrane protein that has multiple functions depending on the ligand it is binding, and it is involved in various signaling pathways, including the Wnt/β-catenin pathway. Given that β-catenin influences stemness and acts downstream of CD44, we hypothesized that TSG-6 interacts with the CD44 receptor and stimulates β-catenin to activate YAP-1 during TSG-6-mediated transdifferentiation of HSCs. Immunoprecipitation assays showed the interaction of TSG-6 with CD44, and immunofluorescence staining analyses revealed the colocalization of TSG-6 and CD44 at the plasma membrane of TSG-6-treated pHSCs. In addition, TSG-6 treatment upregulated the inactive form of phosphorylated glycogen synthase kinase (GSK)-3β, which is a negative regulator of β-catenin, and promoted nuclear accumulation of active/nonphosphorylated β-catenin, eventually leading to the activation of YAP-1. However, CD44 suppression in pHSCs following CD44 siRNA treatment blocked the activation of β-catenin and YAP-1, which inhibited the transition of TSG-6-treated HSCs into stem-like cells. Therefore, these findings demonstrate that TSG-6 interacts with CD44 and activates β-catenin and YAP-1 during the conversion of TSG-6-treated pHSCs into stem-like cells, suggesting that this novel pathway is an effective therapeutic target for controlling liver disease.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.2
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• pp.97-108
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• 2011

Cancer stem cells have stem cell-like features, such as the ability for self-renewal and differentiation but show unlimited growth because they have the lost normal regulation of cell growth. Cancer stem cells and normal stem cells have similar features. They show high motility, diversity of progeny, robust proliferative potential, association with blood vessels, immature expression profiles, nestin expression, epidermal growth factor (EGF)-receptor expression, phosphatase and tensin homolog (PTEN) expression, hedgehog pathway activity, telomerase activity, and Wnt pathway activity. On the other hand, with cancer cells, some of these signaling pathways are abnormally modified. In 1875, Cohnheim suggested the concept of cancer stem cells. Recently, evidence for the existence of cancer stem cells was identified. In 1994, the cancer stem cells' specific cell surface marker for leukemia was identified. Since then, other specific cell surface markers for cancer stem cells in solid tumors (e.g. breast and colon cancer) have been identified. In oral cancer, studies on cancer stem cells have been performed mainly with squamous cell carcinomas. Oral cancer specific cell surface markers, which are genes strongly expressed in oral cancer and cancer stem cell specific side populations, have been identified. Cancer stem cells are resistant to radiotherapy and chemotherapy. Therefore, to eliminate malignant tumors efficiently and reduce the recurrence rate, therapy targeting cancer stem cells needs to be performed. Currently, studies targeting the cancer stem cells' specific signaling pathways, telomerase and tumor vasculatures are being done.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.52-68
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• 2008

Objectives and Methods : Salviae miltiorrhizae Radix (SMR) promotes blood circulation to remove blood stasis, cools the blood to relieve carbuncle, clears away heat from the heart and tranquilizes the mind. This study was designed to investigate the effects of SMR on immuno-potentiative action in terms of changes in the genetic profile of dendritic cells (DC) using by microarray analysis. Results and Conclusion: In this experiment, treatments with more than 250 ${\mu}g/ml$ upto 1000 ${\mu}g/ml$ of SMR elevated the proliferation rates of DC. Microscopic observations confirmed the tendency on proliferation rates. Expression levels of genes related with cellular methabolic process, cell communication, and macromolecule metabolic process were elevated by treatment with SMR in comparison of functional distribution in a Biological Process. In molecular functions, expression levels of genes related with receptor activation, nucleotide binding and nucleic acid binding were elevated. In cellular components, expression levels of genes related to cellular membrane-bound organelles were elevated. In addition, expression levels of genes related to Wnt signalling pathways and the glycerophospholipid metabolism were elevated through analysis using pathway analysis between up-and down-regulated genes in cells treated with SMR. Finally, genes related to JAK2, GRB2, CDC42, SMAD4, B2M, FOS and ESRI located the center of Protein interaction network of genes through treatment with SMR.

• BMB Reports
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• v.45 no.8
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• pp.427-432
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• 2012

Primary cilia, single hair-like appendage on the surface of the most mammalian cells, were once considered to be vestigial cellular organelles for a past century because of their tiny structure and unknown function. Although they lack ancestral motility function of cilia or flagella, they share common ground with multiciliated motile cilia and flagella on internal structure such as microtubule based nine outer doublets nucleated from the base of mother centrioles called basal body. Making cilia, ciliogenesis, in cells depends on the cell cycle stage due to reuse of centrioles for cell division forming mitotic spindle pole (M phase) and assembling cilia from basal body (starting G1 phase and maintaining most of interphase). Ciliary assembly required two conflicting processes such as assembly and disassembly and balance between these two processes determines the length of cilia. Both process required highly conserved transport system to supply needed substance to grow tip of cilia and bring ciliary turnover product back to the base of cilia using motor protein, kinesin and dynein, and transport protein complex, IFT particles. Disruption of ciliary structure or function causes multiple human disorder called ciliopathies affecting disease of diverse ciliated tissues ranging from eye, kidney, respiratory tract and brain. Recent explosion of research on the primary cilia and their involvement on animal development and disease attracts scientific interest on how extensively the function of cilia related to specific cell physiology and signaling pathway. In this review, I introduce general features of primary cilia and recent progress in understanding of the ciliary length control and signaling pathways transduced through primary cilia in vertebrates.

• BMB Reports
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• v.48 no.12
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• pp.668-676
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• 2015

Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways.

• Genomics & Informatics
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• v.9 no.3
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• pp.93-101
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• 2011

The Hairless (HR ) gene regulates the expression of several target genes as a transcriptional corepressor of nuclear receptors. The hair follicle (HF), a small independent organ of the skin, resides in the epidermis and undergoes regenerative cycling for normal hair formation. HF development requires many genes and signaling pathways to function properly in time and space, one of them being the HR gene. Various mutations of the HR gene have been reported to cause the hair loss pheno-type in rodents and humans. In recent studies, it has been suggested that the HR gene is a critical player in the regulation of the hair cycle and, thus, HF development. Furthermore, the HR gene is associated with the Wnt signaling pathway, which regulates proliferation and differentiation of cells and plays an essential role in hair and skin development. In this review, we summarize the mutations responsible for human hair disorders and discuss the roles of the HR gene in HF development.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6201-6206
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• 2015

The epithelial-mesenchymal transition (EMT) is a cellular process though which an epithelial phenotype can be converted into a phenotype of mesenchymal cells. Under physiological conditions EMT is important for embryogenesis, organ development, wound repair and tissue remodeling. However, EMT may also be activated under pathologic conditions, especially in carcinogenesis and metastatic progression. Major signaling pathways involved in EMT include transforming growth factor ${\beta}(TGF-{\beta})$, Wnt, Notch, Hedgehog and other signaling pathways. These pathways are related to several transcription factors, including Twist, Smads and zinc finger proteins snail and slug. These interact with each other to provide crosstalk between the relevant signaling pathways. This review lays emphasis on studying the relationship between EMT and signaling pathways in carcinogenesis and metastatic progression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2789-2800
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• 2013

Background: The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. Material and Method: A systematic literature search was performed for original articles published from January 2007 until May 2012. Results: Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. $Wnt/{\beta}$-catenin signaling pathway has been also evidenced to be an attractive CSC-target. Conclusions: This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

• Journal of Veterinary Clinics
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• v.26 no.5
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• pp.429-432
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• 2009

Aberrant translocation of ${\beta}$-catenin can be induced by the dissociation of cadherin-catenin complex, which is mediated by the activation of receptor tyrosine kinases (RTKs). We examined the expression levels of MET/RON RTKs in tissue samples of canine cutaneous melanotic tumor. The activation of MET/RON RTKs was observed in 28% of the examined samples. Our results indicate the possibility that the activated MET/RON RTKs are implicated in the dissociation of cadherin-catenin complex in canine cutaneous melanotic tumor.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1534-1540
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• 2005

In order to testify the urate lowering effects of Daihwangmudan-tang(DMT), ICR mice were injected monosodium urate into the abdominal cavity and then DMT was administered on 2 and 4 days after Injection. Uric acid and triglyceride were measured as hematological indices of gout, and some genes related with this change were identified by ACP based GeneFishing PCR method and direct sequencing. From this experiment, DMT highly decreased the blood levels of uric acid and significantly suppressed and lowered the acute increment of triglyceride level. There were 11 differentially expressed genes(DEG) having relations with positive actions of DMT, and 4 major genes in the middle of DEGs were sequenced; Mfap 2, jagged 2, Hsd17b7, DkkI-1, These genes were supposed that several mechanisms through interleukin 1 and T-cell anergy, LDL cholesterol metabolism, wnt pathway would be related with the anti-inflammation effect against gout.