https://scholar.dgist.ac.kr/handle/20.500.11750/336 2026-04-04T16:37:37Z 2026-04-04T16:37:37Z Kong, Jin-Sun Park, Jihwan Yoo, Seung-Ah Koh, Jung Hee Hwang, Daehee Kim, Wan-Uk https://scholar.dgist.ac.kr/handle/20.500.11750/59009 2025-09-01T11:10:11Z 2017-11-05T15:00:00Z

Title: Identification of Key Regulators for Resolution of Chronic Inflammatory Arthritis through a Systems Approach Author(s): Kong, Jin-Sun; Park, Jihwan; Yoo, Seung-Ah; Koh, Jung Hee; Hwang, Daehee; Kim, Wan-Uk Abstract: Background/Purpose: Collagen-induced arthritis(CIA), a representative animal model of chronic inflammatory arthritis, follows phases of induction, peak of inflammation and resolution. This study aims to identify the key regulator genes that change with time course in animal models of rheumatoid arthritis through dynamics analysis. Methods: We first investigated gene expression profiles in the synovial tissues of mice with CIA at early, peak, resolution phase of arthritis using microarray analysis and identified differentially expressed genes (DEGs) associated with arthritis resolution. We built a resolution-associated network model describing interactions among these DEGs and then selected three hub-like genes from the network model, which can significantly contribute to regulating function of the resolution-associated network. We examined the level of gene expression in the synovial tissues and the function of selected genes in resolution of CIA. Results: From time-course gene expression profiles of CIA synovial tissues, we identified 2237 resolution-related genes, and found that these genes were significantly associated with Toll-like receptor and T and B cell receptor signaling pathways. Network analysis of these resolution-related genes further selected three hub genes, Itgb1, RPS3 and YwhaZ, that can be predominantly responsible for arthritis resolution. These genes were highly expressed in independent synovial tissues at resolution phase. Particularly, the expression of Itgb1, RPS3 and YwhaZ was elevated in regulatory T cells and alternatively-activated macrophages (M2) that are involved in restoration of chronic inflammation. Moreover, recombinant Itgb1, RPS3, and YwhaZ dose-dependently reduced pro-inflammatory cytokine expression in peritoneal macrophages and splenocytes. To test a potential application of proteins from selected genes for detecting the arthritis resolution, the levels of proteins from the selected genes also were analyzed in mice serum and urine of patients with rheumatoid arthritis (RA). As a result, serum YwhaZ concentration was higher at resolution phase than at peak phase among the three proteins from selected genes. Additionally, YwhaZ concentrations in the urine of patients with rheumatoid arthritis were associated with the degree of treatment response; YwhaZ levels increased significantly after treatment in good response group (n=23) while the protein level before and after treatment were not different in moderate (n=12) or none (n=25) response group. Conclusion: Our comprehensive analysis of gene profile contributing to arthritis resolution reveals novel anti-arthritic genes, tgb1, RPS3, and YwhaZ. We anticipate that tgb1, RPS3 and YwhaZ will be novel targets for predict the arthritis resolution and could be therapeutic targets for choric inflammatory arthritis.

2017-11-05T15:00:00Z 김효정 임준현 Timilsina, Rupak 박지환 홍성현 Jung, Sukjoon 김진희 Woo, Hye Ryun Lim, Pyung Ok Hwang, Daehee Nam, Hong Gil https://scholar.dgist.ac.kr/handle/20.500.11750/47177 2025-07-25T04:09:29Z 2017-07-23T15:00:00Z

Title: How do plants age and die - some new insights Author(s): 김효정; 임준현; Timilsina, Rupak; 박지환; 홍성현; Jung, Sukjoon; 김진희; Woo, Hye Ryun; Lim, Pyung Ok; Hwang, Daehee; Nam, Hong Gil

2017-07-23T15:00:00Z Kwon, Min Jee Han, Myeong Hoon Joshua A. Bagley Hyeon, Do Young Ko, Byung Su Lee, Yun Mi Cha, InJun Kim, SeungYeol Kim, Dong Young Kim, Ho Min Hwang, Daehee Lee, Sung-Bae Yuh Nung Jan https://scholar.dgist.ac.kr/handle/20.500.11750/14370 2025-07-25T02:34:41Z 2019-07-11T15:00:00Z

Title: Coiled coil structure-dependent interactions between polyQ proteins and Foxo contribute to dendrite defects Author(s): Kwon, Min Jee; Han, Myeong Hoon; Joshua A. Bagley; Hyeon, Do Young; Ko, Byung Su; Lee, Yun Mi; Cha, InJun; Kim, SeungYeol; Kim, Dong Young; Kim, Ho Min; Hwang, Daehee; Lee, Sung-Bae; Yuh Nung Jan Abstract: Neurodegenerative disorders, such as Huntington's diseases and spinocerebellar ataxias (SCAs), are driven by proteins with expanded polyglutamine (polyQ) tracts. Recently, coiled-coil structures in polyQ regions of such proteins were shown to facilitate aggregate formation and ultimately lead to cell death. However, the molecular mechanism linking these structural domains to neuronal toxicity of polyQ proteins remains elusive. Here, we demonstrate that coiled-coil structures in the Q repeat region of SCA type 3 (SCA3) polyQ proteins confer protein toxicity in Drosophila neurons. To functionally characterize coiled-coil structures in the Q repeat regions, we generated three structural variants of SCA3 polyQ proteins: (i) MJDtr-76Q, containing both α-helical coiled-coil and β-sheet hairpin structures in the Q repeat region; (ii) MJDtr-70Q_cc0, possessing only α-helical coiled-coil structures due to the incorporation of β-sheet-breaking residues (Q-to-N or Q-to-E mutations); and (iii) MJDtr-70Q_pQp, with no secondary structure due to the introduced proline residues (Q-to-P mutations). Through comparative analysis of these variants, we found that coiled-coil structures facilitated nuclear localization of SCA3 polyQ proteins and induced dendrite defects in Drosophila dendritic arborization neurons. Furthermore, genetic and functional screening identified the transcription factor Foxo as a target of polyQ proteins, and coiled-coil-mediated interactions of Foxo and polyQ proteins in the nucleus resulted in the observed dendrite and behavioral defects in Drosophila These results demonstrate that coiled-coil structures of polyQ proteins are crucial for their neuronal toxicity, which is conferred through coiled-coil to coiled-coil interactions with the nuclear targets of these proteins.

2019-07-11T15:00:00Z