• Archives of Pharmacal Research
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• v.22 no.1
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• pp.1-8
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• 1999

Transforming growth factor-$\beta$ (TGF-$\beta$) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiations as well as a number of basic physiological functions. The effects of TGF-$\beta$ are critically dependent on the expression and distribution of a family of TGF-$\beta$ receptors, the TGF-$\beta$ types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. the coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-$\beta$ RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-$\beta$ RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-$\beta$ RII gene may be a very critical step in the pathway of carcinogenesis.

• BMB Reports
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• v.38 no.1
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• pp.9-16
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• 2005

Transforming Growth Factor (TGF)-$\beta$ family, including TGF-$\beta$, bone morphorgenic protein (BMP), and activn, plays an important role in essential cellular functions such as proliferation, differentiation, apoptosis, tissue remodeling, angiognesis, immune responses, and cell adhesions. TGF-$\beta$ predominantly transmits the signals through serine/threonine receptor kinases and cytoplasmic proteins called Smads. Since the discovery of TGF-$\beta$ in the early 1980s, the dysregulation of TGF-$\beta$/Smad signaling has been implicated in the pathogenesis of human diseases. Among signal transducers in TGF-$\beta$/Smad signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative regulators forming autoinhibitory feedback loops and mediate the cross-talking with other signaling pathways. Expressions of I-Smads are mainly regulated on the transcriptional levels and post-translational protein degradations and their intracellular levels are tightly controlled to maintain the homeostatic balances. However, abnormal levels of I-Smads in the pathological conditions elicit the altered TGF-$\beta$ signaling in cells, eventually causing TGF-$\beta$-related human diseases. Thus, exploring the molecular mechanisms about the regulations of I-Smads may provide the therapeutic clues for human diseases induced by the abnormal TGF-$\beta$ signaling.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.222-229
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• 2009

Our previous finding that pre-initiation treatment of indole-3-carbinol (I3C) represents a chemopreventive effect in dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis has prompted us to test the global expression of genes at an early stage. Rats were continuously fed 300 ppm I3C in their diet at 6 weeks of age and were injected with DMBA at 7 weeks of age, and were sacrificed at 8 weeks of age. Global gene expression analysis using oligonucleotide microarrays was conducted to detect altered genes in DMBA- or DMBA plus I3C-treated mammary glands. Altered genes were identified by fold changes of 1.2 and by t-test (P<0.05) from the log ratios of the hybridization intensity of samples between control (Group 1) and DMBA (Group 2), and from those of samples between DMBA (Group 2) and DMBA plus I3C (Group 3). From these genes, we chose altered genes that were up- or down-regulated by DMBA treatment and recovered to the control level by I3C treatment. For early stage of carcinogenesis, I3C treatment induced the recovery to normal levels of several genes including cell cycle pathway (cyclin B2, cell division cycle 2 homolog A), MAP signaling pathway (fibroblast growth factor receptor 1, platelet derived growth factor receptor, beta polypeptide), and insulin signaling (protein phosphatase 1, regulatory (inhibitor) subunit 3B and flotillin 2), which were up-regulated by DMBA treatment. In addition, I3C treatment induced the recovery to normal levels of several genes including those of MAPK signaling (transforming growth factor, beta receptor 1 and protein phosphatase 3, catalytic subunit, beta isoform), which were down-regulated by DMBA treatment. These results suggest that the targeting of these genes presents a possible approach for chemoprevention in DMBA-induced mammary carcinogenesis.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.11
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• pp.1546-1552
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• 2002

Proliferation and differentiation of ovarian cells are regulated by gonadotrophins and various intraovarian factors, with many of their actions dependent on growth factors. Transforming growth factor-$\beta$ (TGF-$\beta$) has been reportedly involved in the regulation of ovarian follicular development. The overall objectives of the present study were to examine the influence of TGF-$\beta$1 expression in ovarian follicular development or yolk formation and to investigate the association of egg weight with ovarian TGF-$\beta$1 expression at 60 wk. Egg weights of 70 Korean Native Ogol Chicken (KNOC) were recorded from 20 to 60 wk. Ovaries were taken at 60 wk, and TGF-$\beta$1 was measured with ELISA, respectively. Based on egg weight up to 60 wk and TGF-$\beta$1 expression in ovary, the chickens were divided into high and low groups. Egg weights and follicle weight in the high TGF-$\beta$1 group were higher than those in the low groups. Also, TGF-$\beta$1 expression and follicle weight in high egg weight group were higher than those in the low groups. Taken together, the results indicate that TGF-$\beta$1 is associated with egg weight in KNOC. This association of TGF-$\beta$1 with egg weight in KNOC supports the report that TGF-$\beta$ is mainly involved in the development and differentiation of follicles in the poultry. Further studies about other endocrine factors related to yolk formation are required to fully understand the endocrine mechanism of egg weight in Korean Native Ogol Chickens.

• The Journal of Korean Academy of Prosthodontics
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• v.52 no.4
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• pp.298-304
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• 2014

Purpose: This preliminary rabbit study was conducted to evaluate the effect of recombinant human transforming growth factor-${\beta}2$ (rhTGF-${\beta}2$)/poly lactic-co-glycolic acid (PLGA) coating on osseointegration of the titanium (Ti) implant. Materials and methods: Eight Ti implants were anodized with 300 voltages for three minutes. Four of those were coated with rhTGF-${\beta}2$/PLGA by an electrospray method as the experimental group. The implants were placed into tibiae of four New Zealand rabbits, two implants per a tibia, one implant per each group. After 3 and 6 weeks, every two rabbits were sacrificed and micro-computed tomography (microCT) was taken for histomorphometric analysis. Results: In scanning electron microscope (SEM) image, the surface of rhTGF-${\beta}2$/PLGA coated Ti implant showed well distributed particles. Although statistically insignificant, microCT analysis showed that experimental group has higher bone volume / total volume (BV/TV) and trabecular thickness (Tb.Th) values relatively. Cross sectional view also showed more newly formed bone in the experimental group. Conclusion: In the limitation of this study, rhTGF-${\beta}2$/PLGA particles coating on the Ti implant show the possibility of more favorable quantity of newly formed bone after implant installation.

• Journal of Life Science
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• v.22 no.2
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• pp.133-141
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• 2012

In this study, we established a radiodermatitis animal model and investigated the change in immune cell proportions in the secondary lymphoid organs. The cells responsible for the increased transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and interleukin-10 (IL-10) production in the lesions following irradiation were also investigated. The radiodermatitis model was constructed by locally exposing the posterior dorsal region of hairless-1 (HR-1) mice to 10 Gy electron (E)-ray/day for six consecutive days. The change in immune cell proportions was analyzed by FACS. Immunohistochemistry was carried out to detect the expression of cytokines and cell-specific markers in the skin. The proportions of antigen-presenting cells, T cells, and B cells in the lymph nodes and spleen were affected by E-irradiation. After irradiation, TGF-${\beta}1$ and IL-17 were co-localized in the papillary region of the dermis with keratin-14 (K-14)-positive cells rather than with regulatory T cells (Treg). IL-10 was not co-stained with Treg, T helper 17 (Th17) cells, dendritic cells, or macrophages. Our data indicate that TGF-${\beta}1$ is over-expressed mainly by proliferated keratinocytes in the lesions of a radiodermatitis animal model.

• CELLMED
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• v.4 no.1
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• pp.3.1-3.8
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• 2014

Spa represents a treatment widely used in many rheumatic diseases (RD). The mechanisms by which immersion in mineral or thermal water ameliorates RD are not fully understood. The net benefit is probably the result of a combination of factors, among which the mechanical, thermal and chemical effects are most prominent. Buoyancy, immersion, resistance and temperature play important roles. According to the gate theory, pain relief may be due to the pressure and temperature of the water on skin; heat may reduce muscle spasm and increase the pain threshold. Mud-bath therapy increases plasma ${\beta}$-endorphin levels and secretion of corticotrophin, cortisol, growth hormone and prolactin. It has recently been demonstrated that thermal mud-bath therapy induces a reduction in circulating levels of prostaglandin E2, leukotriene B4, interleukin-$1{\beta}$ and tumour necrosis factor-${\alpha}$, important mediators of inflammation and pain. Furthermore, balneotherapy has been found to cause an increase in insulin-like growth factor-1, which stimulates cartilage metabolism, and transforming growth factor-${\beta}$. Beneficial anti-inflammatory and anti-degenerative effects of mineral water were confirmed in chondrocytes cultures, too. Various studies in vitro and in humans have highlighted the positive action of mud-packs and thermal baths, especially sulphurous ones, on the oxidant/antioxidant system. Overall, thermal stress has an immunosuppressive effect. Many other non-specific factors may also contribute to the beneficial effects observed after spa therapy in some RD, including effects on cardiovascular risk factors (e.g. adipokines) and changes in the environment, pleasant surroundings and the absence of work duties.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.4
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• pp.477-484
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• 2019

Objective: We aimed to observe hair follicle (HF) development in the dorsal skin and elucidate the expression patterns of genes and proteins related to skin and HF development in Rex rabbits from birth to 8 weeks of age. Methods: Whole-skin samples were obtained from the backs of Rex rabbits at 0, 2, 4, 6, and 8 weeks of age, the morphological development of primary and secondary HFs was observed, and the gene transcript levels of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), bone morphogenetic protein 2 (BMP2), transforming growth factor ${\beta}-1$, 2, and 3 ($TGF{\beta}-1$, $TGF{\beta}-2$, and $TGF{\beta}-3$) were examined using quantitative real-time polymerase chain reaction (PCR). Additionally, Wnt family member 10b (Wnt10b) and ${\beta}$-Catenin gene and protein expression were examined by quantitative real-time PCR and western blot, respectively. Results: The results showed significant changes in the differentiation of primary and secondary HFs in Rex rabbits during their first 8 weeks of life. The IGF-I, EGF, $TGF{\beta}-2$, and $TGF{\beta}-3$ transcript levels in the rabbits were significantly lower at 2 weeks of age than at birth and gradually increased thereafter, while the BMP2 and $TGF{\beta}-1$ transcript levels at 2 weeks of age were significantly higher than those at birth and gradually decreased thereafter. ${\beta}$-Catenin gene expression was also significantly affected by age, while the Wnt10b transcript level was not. However, the Wnt10b and ${\beta}$-catenin protein expression levels were the lowest at 2 and 4 weeks of age. Conclusion: Our data showed that a series of changes in HFs in dorsal skin occurred during the first 8 weeks. Many genes, such as IGF-I, EGF, BMP2, $TGF{\beta}-1$, $TGF{\beta}-2$, $TGF{\beta}-3$, and ${\beta}$-Catenin, participated in this process, and the related proteins Wnt10b and ${\beta}$-Catenin in skin were also affected by age.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.436-446
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• 2018

Background: The potential therapeutic values of Korean Red Ginseng extract (KRGE) in autoimmune disorders of nervous system have not been fully investigated. Methods: We used an acute experimental autoimmune encephalomyelitis animal model of multiple sclerosis and determined the effects and mechanism of KRGE on spinal myelination. Results: Pretreatment with KRGE (100 mg/kg, orally) for 10 days before immunization with myelin basic protein $(MBP)_{68-82}$ peptide exerted a protective effect against demyelination in the spinal cord, with inhibited recruitment and activation of immune cells including microglia, decreased mRNA expression of detrimental inflammatory mediators (interleukin-6, interferon-${\gamma}$, and cyclooxygenase-2), but increased mRNA expression of protective inflammatory mediators (insulin-like growth factor ${\beta}1$, transforming growth factor ${\beta}$, and vascular endothelial growth factor-1). These results were associated with significant downregulation of p38 mitogen-activated protein kinase and nuclear factor-${\kappa}B$ signaling pathways in microglia/macrophages, T cells, and astrocytes. Conclusion: Our findings suggest that KRGE alleviates spinal demyelination in acute experimental autoimmune encephalomyelitis through inhibiting the activation of the p38 mitogen-activated protein kinase/nuclear factor-${\kappa}B$ signaling pathway. Therefore, KRGE might be used as a new therapeutic for autoimmune disorders such as multiple sclerosis, although further investigation is needed.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.307-314
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• 2013

Connective tissue growth factor (CTGF) is a potent pro-fibrotic factor, which is implicated in fibrosis through extracellular matrix (ECM) induction in diabetic cardiovascular complications. It is an important downstream mediator in the fibrotic action of transforming growth factor ${\beta}$ ($TGF{\beta}$) and is potentially induced by hyperglycemia in human vascular smooth muscle cells (VSMCs). Therefore, the goal of this study is to identify the signaling pathways of CTGF effects on ECM accumulation and cell proliferation in VSMCs under hyperglycemia. We found that high glucose stimulated the levels of CTGF mRNA and protein and followed by VSMC proliferation and ECM components accumulation such as collagen type 1, collagen type 3 and fibronectin. By depleting endogenous CTGF we showed that CTGF is indispensable for the cell proliferation and ECM components accumulation in high glucose-stimulated VSMCs. In addition, pretreatment with the MEK1/2 specific inhibitors, PD98059 or U0126 potently inhibited the CTGF production and ECM components accumulation in high glucose-stimulated VSMCs. Furthermore, knockdown with ERK1/2 MAPK siRNA resulted in significantly down regulated of CTGF production, ECM components accumulation and cell proliferation in high glucose-stimulated VSMCs. Finally, ERK1/2 signaling regulated Egr-1 protein expression and treatment with recombinant CTGF reversed the Egr-1 expression in high glucose-induced VSMCs. It is conceivable that ERK1/2 MAPK signaling pathway plays an important role in regulating CTGF expression and suggests that blockade of CTGF through ERK1/2 MAPK signaling may be beneficial for therapeutic target of diabetic cardiovascular complication such as atherosclerosis.