https://scholar.gist.ac.kr/handle/local/7973 2026-02-01T22:10:15Z https://scholar.gist.ac.kr/handle/local/32672 Title: Upregulation of arginase-II in osteoarthritic chondrocytes: Author(s): Wihak Kim Abstract: Osteoarthritis (OA) is characterized by cartilage destruction and occurs to be related to various metabolic disorders. However, in OA pathogenesis, mechanism of pathological effect of amino acids has not been clearly identified to date. We herein demonstrate that alterations of amino acid metabolism are important to OA pathogenesis in mice. Our microarray analysis showed that arginase-II (Arg-II) expression was significantly increased in mouse chondrocytes under various osteoarthritic conditions. Arg-II was also upregulated in mouse OA chondrocytes induced by various catabolic regulators and in OA cartilage of human and various mouse models. Moreover, Arg-II overexpressed by using Adenoviral systems in mouse chondrocytes and knee joint tissues lead to OA pathogenesis. Our findings demonstrate that Arg-II is a novel catabolic regulator of OA pathogenesis and could be a potential therapeutic target for the treatment of OA. 2018-12-31T15:00:00Z https://scholar.gist.ac.kr/handle/local/19875 Title: Unravelling the anti-cancer mechanism of small molecule drugs that modulate novel target in the tumor microenvironment Author(s): Taejoon Yoon Abstract: The tumor microenvironment (TME) is composed of intratumoral cell groups such as vascular cells, stromal cells or immune cells and even extracellular substrates or hypoxia. Of the many components that compose the TME, cancer-associated fibroblasts (CAF) and tumor-associated macrophage (TAM) are key components. CAF are activated compared to normal, tissue resident fibroblasts. CAF express marker genes and secrete specific cytokines at a greater rate than normal fibroblasts. Moreover, TAM show a phenotype that reflects their tumor origin and is distinct from normal macrophages or related-immune cells. There is an intercellular communication (termed crosstalk) between CAF and TAM than regulate tumor growth and metastasis. Previous research has shown that the cytokines IL-6 or GM-CSF are a key component of the crosstalk between CAF and TAM. In this thesis, FDA approved drugs were screened to select candidates that can target the IL-6 and downstream JAK/STAT signaling pathway in CAF. The MTT assay and ELISA were used to test CAF viability IL-6 cytokine expression, respectively. A hit drug, termed NDT-SOR, was selected as a best candidate. NDT-SOR downregulated IL-6 expression in human CAFs and immortalized hTERT fibroblasts stimulated by cancer cell YD-10B conditioned media (CM). Using western blotting, it was shown that NDT-SOR downregulates the expression of some members of the JAK/STAT pathway. Using co-culture assays with CAF, NDT-SOR was found to restrict monocyte differentiation and polarization into macrophages. Furthermore, these NDT-SOR treated monocytes showed reduced expression of TAM-specific genes, such as IL-10 or CD-206, compared to normal monocytes after co-culture. Additionally, invasion assay analyses show that NDT-SOR treatment reduced the ability of TAM to induce cancer cell migration. These results indicate that there are some crosstalk between CAF, TAM and cancer cells, and also NDT-SOR was newly discovered to be a drug that could inhibit the crosstalk, confirming the possibility of being a potential drug. 2022-12-31T15:00:00Z https://scholar.gist.ac.kr/handle/local/19844 Title: Toll-like receptor 5 from Ctenopharyngodon idella Author(s): Ham Suah Abstract: TLR5 is a pattern recognition receptor involved in the innate immune response. It is highly expressed on the cell membranes of intestine epithelial cells and dendritic cells, and it is the only human TLR known to bind a protein ligand. The ligand for TLR5 is bacterial flagellin, which binds to TLR5, inducing dimerization and triggering the innate immune response. Consequently, defects in TLR5 can impact inflammatory diseases of the gut, autoimmune diseases, and cancer cell growth. While the structure of zebrafish TLR5-LRR14 VLR in complex with flagellin has been determined through X-ray crystallography, understanding the precise mechanisms of flagellin recognition and signal transduction by TLR5 requires the full-length structure. In this study, I expressed Ctenopharyngodon idella (Grass carp) Toll-like receptor 5a and 5b, and using Cryo-EM, I determined the structures of TLR5a in its apo state, both as a dimer and a tetramer. 2023-12-31T15:00:00Z https://scholar.gist.ac.kr/handle/local/33272 Title: The Study on Cell Migration using Mouse Embryonic Fibroblasts derived from Fxyd5 Deficient Mouse Author(s): Won-Jae Lee Abstract: Cell migration is a process that is an essential mechanism of maintaining cellular homeostasis, thus, contributes to diverse biological functions in the multicellular organism. Aberrant regulation of cell migration drives the progression of diverse diseases including lung fibrosis, autoimmune syndromes, neuronal migration disorders, and cancer metastasis. Therefore, identifications of the factors that control cell migration are important. FXYD domain-containing ion transport regulator 5 (FXYD5), a modulator of ion transport or Na, K-ATPase, is correlated with various types of cancers and is associated with cancer cell invasion. FXYD5 down-regulates E-cadherin and progress cancer metastasis. Although studies on FXYD5 in various types of cancer has been actively conducted, studies on biological function of FXYD5 in normal cells are insufficient. In this study, the biological roles of Fxyd5 on cell migration were examined using Fxyd5 knock-out mice. Mouse embryonic fibroblasts (MEFs) were isolated to compare between wild-type and knock-out of Fxyd5 (Fxyd5-/-) groups. Then, collective cell migration, single cell migration, and morphological changes of single cell were identified using wild-type and Fxyd5-/- MEFs. As a result, knock-out of Fxyd5 attenuated chemotaxis in response to chemoattractant gradient in transwell migration assay and prolonged in vitro wound closure time, indicating that deletion of Fxyd5 decreased collective cell migration, in wound-healing assay. Also, knock-out of Fxyd5 reduced single cell migration capacity by decreasing the speed and distance of moving cells. In light of this, further microscope observations revealed that depletion of Fxyd5 decreased the density and length of filopodia, which is a fundamental protrusive structure at the leading edge of motile cells. Taken together, Fxyd5 functions as an essential factor of collective cell migration and single cell migration. These results should help a better understanding of the biological functions of the Fxyd5 on cell migration. 2020-12-31T15:00:00Z