Hei Jung Kim

Kyungpook National University, Daikyū, Daegu, South Korea

Are you Hei Jung Kim?

Claim your profile

Publications (14)43.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4(+) T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN- γ, TNF- α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.
    Biochemical and Biophysical Research Communications 09/2014; · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis is an important biological process during development, reproduction, and in immune responses. Placental growth factor (PlGF) is a member of vascular endothelial growth factor that is critical for angiogenesis and vasculogenesis. We generated transgenic mice overexpressing PlGF in specifically T cells using the human CD2-promoter to investigate the effects of PlGF overexpression.
    Arteriosclerosis Thrombosis and Vascular Biology 08/2014; · 6.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1's role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.
    Biochemical and Biophysical Research Communications 12/2013; · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the role of Roquin, a RING-type ubiquitin ligase family member, we used transgenic mice having enforced Roquin expression in T cells, with collagen-induced arthritis (CIA). Wild-type (WT) and Roquin transgenic (Tg) mice were immunized with bovine type-II collagen (CII). Arthritis severity was evaluated by clinical score, histopathologic CIA severity, pro-inflammatory and anti-inflammatory cytokine levels, anti-CII antibody levels, and populations of Th1, Th2, germinal center B cells, and follicular helper T cells in CIA. T-cell proliferation in vitro and cytokine levels were determined to assess the response to CII. Roquin Tg mice developed more severe CIA and joint destruction compared with WT mice. Production of TNF-α, IFN-γ, IL-6 and pathogenic anti-collagen CII-specific IgG and IgG2a antibodies was increased in Roquin Tg mice. In addition, in vitro T-cell assays showed increased proliferation and pro-inflammatory cytokine production in response to CII as a result of enforced Roquin expression in T cells. Furthermore, the Th1/Th2 balance was altered by an increased Th1 and decreased Th2 population. These findings suggest that overexpression of Roquin exacerbates the development of CIA and enforced expression of Roquin in T cells may promote autoimmune diseases such as CIA.
    Journal of Biological Chemistry 10/2012; · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular- superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC- SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1β, TNFα, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.
    Experimental and Molecular Medicine 06/2012; 44(9):529-35. · 2.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Calcineurin (CN) is a calcium- and calmodulin-dependent serine/threonine phosphatase. In immune cells, CN controls the activity of a wide range of transcription factors, including nuclear factor of activated T, nuclear factor-kappa B, c-fos, and Elk-1. CN plays an important role in synoviocyte activation and arthritis progression in vivo and this function is tightly linked to dysregulated intracellular Ca(2+) store and Ca(2+) response triggered by proinflammatory cytokines. In the present study, transgenic mice expressing human calcineurin-binding protein 1 (hCabin1) were generated, driven by type II collagen promoter, and the efficiency of these mice was investigated by experimental arthritis. These transgenic mice successfully expressed hCabin1 in joint tissue as well as other organs such as liver, heart, and brain. The overexpression of hCabin1 reduced the disease severity during collagen-induced arthritis. In fibroblast-like synoviocytes (FLSs) from hCabin1 transgenic mice, the productions of these cytokines, including interleukin (IL)-2, IL-4, and IFN-γ, were decreased and matrix metalloproteinases were also depressed in transgenic mice FLS. In addition, these effects were only found in the joint tissue, which is a major inflammation site. These findings will provide a better knowledge of the pathogenic mechanisms of rheumatoid arthritis and a potential animal model of the chronic inflammatory conditions, including atherosclerosis and transplantation.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 12/2011; 32(1):6-11. · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atopic dermatitis (AD) is a chronically relapsing, noncontagious pruritic skin disease with two phases: acute and chronic. Previous studies have shown that the cysteine protease cathepsin S (CTSS) is linked to inflammatory processes, including atherosclerosis and asthma. The possibility that this or other cysteine proteases might cause itching or be part of a classical ligand-receptor signaling cascade has not been previously considered. Recently, CTSS was shown to be a ligand for proteinase-activated receptor-2 (PAR-2), which is associated with itching. In this study, we show that CTSS-overexpressing transgenic (TG) mice spontaneously develop a skin disorder similar to chronic AD. The results of this study suggest that CTSS overexpression triggers PAR-2 expression in dendritic cells (DCs), resulting in the promotion of CD4(+) differentiation, which is involved in major histocompatibility complex (MHC) class II expression. In addition, we investigated mast cells and macrophages and found significantly higher mean levels of T helper type 1 (Th1) cell-associated cytokines than T helper type 2 (Th2) cell-associated cytokines in CTSS-overexpressing TG mice. These results suggest that increased PAR-2 expression in DCs as a result of CTSS overexpression induces scratching behavior and Th1 cell-associated cytokine expression, and can trigger chronic AD symptoms.
    Journal of Investigative Dermatology 12/2011; 132(4):1169-76. · 6.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The T-cell receptor (TCR) engages with an antigen and initiates a signaling cascade that leads to the activation of transcription factors. Roquin, a protein encoded by the RC3H1 gene and characterized as an immune regulator, was recently identified as a novel RING-type ubiquitin ligase family member, but the mechanisms by which Roquin regulates T-cell responses are unclear. We used the EL-4 murine lymphoma cell line to elucidate the role of Roquin in vitro. Roquin-overexpressing EL-4 cells became hyper-responsive after anti-CD3/CD28 stimulation in vitro and were a major source of the cytokines IL-2 and TNF-α. Upon activation, these cells showed particularly enhanced production of IL-2 and TNF-α. To clarify the important role played by Roquin in T-cell responses ex vivo, we generated T-cell-specific Roquin transgenic (Tg) mice. Roquin-Tg CD4(+) T-cells showed enhanced production of IL-2 and TNF-α in response to TCR stimulation with anti-CD28 co-stimulation. Further studies are necessary to investigate the role of Roquin in the regulation of primary T-cell activation, survival, and differentiation.
    Biochemical and Biophysical Research Communications 11/2011; 417(1):280-6. · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The transcription factor Juxtaposed with another zinc finger gene 1 (JAZF1) is a zinc finger protein that binds to the nuclear orphan receptor TR4. Recent evidence indicates that TR4 receptor functions as both a positive and negative regulator of transcription, but the role of JAZF1 in transcriptional mechanisms has not been elucidated. Recently, the incidence rate of congenital heart malformations was reported to be significantly elevated in patients who had neurofibromatosis 1 (NF1) with chromosomal microdeletion syndrome. Furthermore, Joined to JAZF1 (SUZ12) is expressed at high levels in the hearts of adult patients with NF1 microdeletion syndrome. Therefore, we hypothesized that ectopic expression of JAZF1 may lead to cardiac malformations that deleteriously affect the survival of neonates and adults. We sought to elucidate the role of JAZF1 in cardiac development using a Jazf1-overexpressing (Jazf1-Tg) mouse model. In Jazf1-Tg mice, Jazf1 mRNA expression was significantly elevated in the heart. Jazf1-Tg mice also showed cardiac defects, such as high blood pressure, electrocardiogram abnormalities, apoptosis of cardiomyocytes, ventricular non-compaction, and mitochondrial defects. In addition, we found that the expression levels of pro-apoptotic genes were elevated in the hearts of Jazf1-Tg mice. These findings suggest that Jazf1 overexpression may induce heart failure symptoms through the upregulation of pro-apoptotic genes in cardiomyocytes.
    Transgenic Research 01/2011; 20(5):1019-31. · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/beta-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which has Galpha subunits with GTPase activity, inhibits the Wnt/beta-catenin signal through inactivation of Galpha(o). In the present study, the effects of RGS19 on mouse cardiac development were observed. In P19 teratocarcinoma cells with RGS19 overexpression, RGS19 inhibited cardiomyocyte differentiation by blocking the Wnt signal. Additionally, several genes targeted by Wnt were down-regulated. For the in vivo study, we generated RGS19-overexpressing transgenic (RGS19 TG) mice. In these transgenic mice, septal defects and thin-walled ventricles were observed during the embryonic phase of development, and the expression of cardiogenesis-related genes, BMP4 and Mef2C, was reduced significantly. RGS19 TG mice showed increased expression levels of brain natriuretic peptide and beta-MHC, which are markers of heart failure, increase of cell proliferation, and electrocardiogram analysis shows abnormal ventricle repolarization. These data provide in vitro and in vivo evidence that RGS19 influenced cardiac development and had negative effects on heart function.
    Journal of Biological Chemistry 09/2010; 285(37):28627-34. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The major objective of this study was to improve the development rate of parthenogenetic porcine embryos. In this study, the anti-oxidative and anti-apoptotic effects of three antioxidants, β-mercaptoethanol (β-ME), α-tocopherol, and extracellular superoxide dismutase (EC-SOD), were examined on the development of parthenogenetic porcine embryos. The development rate of parthenogenetic porcine embryos to the blastocyst stage was 8.1% for control; 19.1%, 14.6%, and 5.0% for 1, 3, and 5 μM β-ME; 17.2% and 17.5% for 50 and 100 μM α-tocopherol and 12.0% and 4.0% for EC-SOD transgenic mouse embryonic fibroblast (Tg-MEF) and EC-SOD non-transgenic mouse embryonic fibroblast (NTg-MEF) conditioned medium at day 3, respectively. Here, β-ME, α-tocopherol, and EC-SOD Tg-MEF conditioned medium increased the development rate of parthenogenetic porcine embryos to the blastocyst stage (P < 0.05). The average number of total cells and apoptotic cells at the blastocyst was analyzed at the optimal conditions of the three antioxidants. The three antioxidants increased the average number of total cells at the blastocyst, and they decreased apoptotic cells at the blastocyst as compared to control without supplementation (P < 0.05). When the reactive oxygen species levels in two-cell embryos after 1 μM β-ME and 100 μM α-tocopherol treatment were examined, those were lower than control group (P < 0.05). In conclusion, it was found that the three antioxidants, β-mercaptoethanol, α-tocopherol, and EC-SOD Tg-MEF, conditioned medium can play a role as a strong stimulator in the development of parthenogenetic porcine embryos.
    In Vitro Cellular & Developmental Biology - Animal 11/2009; 46(2):148-54. · 1.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The circling (cir/cir) mouse is one of the murine models for human non-syndromic deafness DFNB6. The mice have abnormal circling behavior, suggesting a balanced disorder and profound deafness. The causative gene was transmembrane inner ear (tmie) gene of which the mutation is a 40-kb genomic deletion including tmie gene itself. In this study, tmie-overexpression trasngenic mice were established. Individuals with germline transmission have been mated with circling homozygous mutant mice (cir/cir) in order to produce the transgenic mutant mice (cir/cir-tg) as a gene therapy. After the genotyping, phenotypic analyses were performed so that the insertion of the new gene might compensate for the diseases such as hearing loss, circling behavior, or swimming inability. Some individuals exhibited complete recovery in their behavior and hearing but the others did not show any amelioration in behavior or hearing. Individual mice had very different levels of tmie transgene expression in the cochlea. These results clearly indicate that tmie protein plays an important role when the appropriate expression level of tmie was expressed in the inner ear. The protein levels were variable in each individual and these are thought to induce the differences in disease amelioration levels.
    Biochemical and Biophysical Research Communications 07/2008; 374(1):17-21. · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis is a chronic inflammatory disease. The generation of reactive oxygen species (ROS) within an inflamed joint has been suggested as playing a significant pathogenic role. Extracellular superoxide dismutase (EC-SOD) is a major scavenger enzyme of ROS, which has received growing attention for its therapeutic potential. To investigate the therapeutic effect of EC-SOD in mice with collagen-induced arthritis (CIA), we used mouse embryonic fibroblast (MEF) of transgenic mice that overexpresses EC-SOD on the skin by using hK14 promoter. DBA/1 mice that had been treated with bovine type II collagen were administrated subcutaneous injections of EC-SOD transgenic MEF (each at 1.4 x 10(60 cells) on days 28, 35, and 42 after primary immunization. To test EC-SOD activity, blood samples were collected in each group on day 49. The EC-SOD activity was nearly 1.5-fold higher in the transgenic MEF-treated group than in the nontransgenic MEF-treated group (p < 0.05). The severity of arthritis in mice was scored in a double-blind manner, with each paw being assigned a separate clinical score. The severity of arthritis in EC-SOD transgenic MEF-treated mice was significantly suppressed in the arthritic clinical score (p < 0.05). To investigate the alteration of cytokine levels, ELISA was used to measure blood samples. Levels of IL-1beta and TNF-alpha were reduced in the transgenic MEF-treated group (p < 0.05). Abnormalities of the joints were examined by H&E staining. There were no signs of inflammation except for mild hyperplasia of the synovium in the transgenic MEF-treated group. The proliferation of CII-specific T cells was lower in the transgenic MEF-treated mice than in those in the other groups. The transfer of EC-SOD transgenic MEF has shown a therapeutic effect in CIA mice and this approach may be a safer and more effective form of therapy for rheumatoid arthritis.
    Cell Transplantation 01/2008; 17(12):1371-80. · 4.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing the causative gene, transmembrane inner ear (tmie), for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir -tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir -tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse.
    Nature Precedings