Eun Soo Hwang

Cell lineage specification depends on both gene activation and gene silencing, and in the differentiation of T helper progenitors to Th1 or Th2 effector cells, this requires the action of two opposing transcription factors, T-bet and GATA-3. T-bet is essential for the development of Th1 cells, and GATA-3 performs an equivalent role in Th2 development. We report that T-bet represses Th2 lineage commitment through tyrosine kinase-mediated interaction between the two transcription factors that inte

The osteopontin (Opn) glycoprotein has been implicated in diverse physiological processes, including vascularization, bone formation, and inflammatory responses. Studies of its role in immune responses has suggested that Opn can set the early stage of type-1 immune (cell-mediated) responses through differential regulation of IL-12 and IL-10 cytokine gene expression in macrophages. Although Opn has been suggested to play a role in the development of type-1 immunity, little is known about control

Interleukin (IL)-2 is the predominant cytokine that is produced by naive Th cells in a primary response. It is required for proliferation and differentiation of Th precursor cells into effector cells. Initial high-level IL-2 production is followed by its decline, and the concomitant induction of cytokines that are typical of the differentiated state. Although the factors that are responsible for the early induction of IL-2 are well defined, the mechanisms that are responsible for its down-regula

Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully unde

Myoblast differentiation is indispensable for skeletal muscle formation and is governed by the precisely coordinated regulation of a series of transcription factors, including MyoD and myogenin, and transcriptional coregulators. TAZ (transcriptional coactivator with PDZ-binding motif) has been characterized as a modulator of mesenchymal stem cell differentiation into osteoblasts and adipocytes through its regulation of lineage-specific master transcription factors. In this study, we investigated

Increasing evidence that decreased bone density and increased rates of bone fracture are associated with abnormal metabolic states such as hyperglycemia and insulin resistance indicates that diabetes is a risk factor for osteoporosis. In this study, we observed that TallyHo/JngJ (TH) mice, a polygenic model of type II diabetes, spontaneously developed bone deformities with osteoporotic features. Female and male TH mice significantly gained more body weight than control C57BL/6 mice upon aging. I

Engagement of T cell receptor (TCR) triggers signaling pathways that mediate activation, proliferation, and differentiation of T lymphocytes. Such signaling events are mediated by reactive oxygen species (ROS), including hydrogen peroxide and lipid peroxides, both of which are reduced by glutathione peroxidase 1 (GPx1). We have now examined the role of GPx1 in the activation, differentiation, and functions of CD4(+) T helper (Th) cells. TCR stimulation increased the intracellular ROS concentrati

c-maf is a T helper (Th)2 cell-specific transcription factor, which promotes the differentiation of Th2 cells mainly by an IL-4-dependent mechanism. It remains unclear whether c-maf possesses any IL-4-independent function in regulating the production of Th2 cytokines. Here, we provide evidence demonstrating that c-maf, independent of IL-4, is essential for normal induction of CD25 in developing Th2 cells. The levels of CD25 are significantly higher in developing Th2 cells than in developing Th1

The third lineage of T helper subsets, Th17, has recently been identified as an IL- 17-producing CD4+ Th cell, and its functions and regulatory mechanisms have been extensively characterized in immune responses. Functional studies have provided evidence that Th17 cells are important for the modulation of autoimmune responses, such as chronic asthma, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. Murine Th17 cell differentiation is enhanced by the coordinated functions

Skeletal muscle plays key roles in metabolic homeostasis. Loss of muscle mass, called muscle atrophy exacerbates disease-associated metabolic perturbations. In this study, we characterized the molecular functions and mechanisms underlying regulation of skeletal muscle atrophy induced by denervation. Denervation significantly increased the expression of heme oxygenase-1 (HO-1) and atrogenes in skeletal muscle. Forkhead box protein O1 (FoxO1) drastically increased in atrophied muscle and selective

T-box-containing protein expressed in T cells (T-bet) is a master transcription factor for the development of interferon (IFN) gamma-producing T helper 1 (Th1) cells and also functions in other immune cells including natural killer (NK), cytotoxic T lymphocytes and dendritic cells. T-bet-deficient mice increased susceptibility to viral infection and tumor development due to the defective functions of immune cells. T-bet is known to play a key role in NK-mediated antimetastatic response; however,

Osteoporosis is a degenerative bone disease characterized by low bone mass and is caused by an imbalance between osteoblastic bone formation and osteoclastic bone resorption. It is known that the bioactive compounds present in green tea increase osteogenic activity and decrease the risk of fracture by improving bone mineral density. However, the detailed mechanism underlying these beneficial effects has yet to be elucidated. In this study, we investigated the osteogenic effect of (-)-epicatechin

Insulin regulates blood glucose levels by binding its receptor and stimulating downstream proteins through the insulin receptor substrate (IRS). Impaired insulin signalling leads to metabolic syndrome, but the regulation of this process is not well understood. Here, we describe a novel insulin signalling regulatory pathway involving TAZ. TAZ upregulates IRS1 and stimulates Akt- and Glut4-mediated glucose uptake in muscle cells. Muscle-specific TAZ-knockout mice shows significantly decreased Irs1