• Title/Summary/Keyword: Transforming growth factor-${\beta}$

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The Role of Tripartite Motif Family Proteins in TGF-β Signaling Pathway and Cancer

  • Lee, Ho-Jae
    • Journal of Cancer Prevention
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    • v.23 no.4
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    • pp.162-169
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    • 2018
  • $TGF-{\beta}$ signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The $TGF-{\beta}$ signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of $TGF-{\beta}$ signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the $TGF-{\beta}$ signaling pathway with relevance to cancer.

Trend of Basic Research for Vocal Fold Scar (성대 반흔에 대한 기초연구의 최신 경향)

  • Lee, Byung-Joo
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.23 no.1
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    • pp.28-32
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    • 2012
  • Vocal fold scar disrupts structure of lamina propria and causes significant change in vocal fold tissue biomechanics, resulting in a range of voice problems that often significantly compromise patient quality of life. Although several therapeutic management have been offered in an attempt to improve vocal fold scar, the ideal treatment has not yet been found. Recently, several tissue engineering technique for vocal fold scar using growth factors, several cells, and scaffolds have been described in tissue culture and animal models. Several growth factors such as hepatocyte growth factor, basic fibroblast growth factor, and transforming growth factor beta 3 for therapy and prevention of vocal fold scar have been studied. Cell types to regenerate vocal folds in scarring tissue have been introduced autologous or scarred vocal fold fibroblast and adult mesenchymal stem cells. Decellularized organ matrix and several hyaluronic acid materials have used as scaffolds for vocal fold scar.

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Tensile stress regulation of NGF and NT3 in human dermal fibroblast

  • Kim, Mi-Na;Hong, Jung-Woo;Nho, Min-Soo;Na, Yong-Joo;Shin, Jennifer Hyun-Jong
    • Proceedings of the KSME Conference
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    • 2008.11a
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    • pp.1585-1587
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    • 2008
  • Fibroblast is constantly subjected to mechanical loads in connective tissues where mechanical signals are converted to intercellular biochemical events. The aim of this study is to understand the effects of tensile stress on the neurotrophin (NT) and transforming growth factor (TGF) expression of fibroblast in vitro. Nerve growth factor (NGF) stimulates fibroblast migration, and TGF is related to tissue repair. In this study, at the uniaxial stretch of 10% strain and frequency of 0.5 Hz, different resting times of 0, 20, and 60 min are placed in between 10 min stimulations periods. Results show increase in NGF mRNA levels and a substantial decrease in NT3 mRNA after 1 hr of stimulation, indicating that the tensile stress may regulate NGF and NT3, key factors for the neurocosmetic applications. The mRNA level for TGF-${\alpha}$ and TGF-${\beta}2$ had increased up to two-folds after 1 hr of stimulation, showing that the tensile stress may control TGF, an important part of wound healing.

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In vitro and In vivo Hair Growth Promotion Effects of Lactobacillus plantarum-Fermented Plant Extracts (MBN) (Lactobacillus plantarum 발효 식물추출물질(MBN)의 in vitro 및 in vivo 발모 효과)

  • Joo, Seong-Soo
    • Korean Journal of Food Science and Technology
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    • v.43 no.3
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    • pp.381-386
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    • 2011
  • This study investigated the effect of herbal extracts fermented by Lactobacillus plantarum (MBN) on hair growth in C57BL/6 mice and HaCaT cells. Five week old mice were applied with MBN topically (0.2 mL) once per for 21 days. Hair regrowth was evaluated by gross examination and verified by hematoxylin-eosin staining. Gene expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), and transforming growth factor-beta1 ($TGF{\beta}1$), relevant to hair growth, were examined. The data revealed that MBN successfully promoted hair growth in both male and female mice at a dose between 200-500 mg/kg and improved hair thickness. The VEGF and KGF genes were expressed in a dose-dependant manner, whereas $TGF{\beta}1$ was not expressed. Moreover, nitric oxide was significantly increased, suggesting an improvement in blood flow. These results indicate that MBN effectively promoted hair growth and gene expression relevant to hair growth in an animal model.

Comparisons of Renoprotective Activities between White Ginseng Radix and Rootlet in Spontaneously Hypertensive Rats with Diabetes

  • Chung, Sung-Hyun;Ko, Sung-Kwon;Park, Se-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.1
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    • pp.57-61
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    • 2002
  • The renoprotective activities of white ginseng radix and rootlet were compared in spontaneously hypertensive rat (SHR) with diabetes. During oral administration of white ginseng radix (Ginseng Radix Alba, GRA) and white ginseng rootlet (Ginseng Radix Palva, GRP) for four weeks, arterial blood pressure and blood glucose levels were determined at every 10 days. In both GRA- and GRP-treatment groups, arterial blood pressures started to go down after 10 days of administration and maintained throughout the study period. After four weeks administrations of GRA and GRP, diastolic blood pressures were significantly decreased with 17% and 9%, respectively. GRA treatment also decreased blood glucose levels after 10 days of administration when compared with diabetic SHR group. At the end of the experiment, serum creatinine (Scr) and blood urea nitrogen (BUN) were not significantly different between the groups, except 62% higher value of BUN in diabetic SHR group when compared with SHR group. In the diabetic SHR group, the excretion of urinary albumin was increased significantly when compared with SHR. The level of urinary albumin in GRA treated group was markedly reduced when compared with diabetic SHR group $(67.8{\pm}4.7\;vs.\;131.3{\pm}13.5\;mg/24\;h).$ To examine the effects of ginseng radices on an overt diabetic nephropathy, index of kidney hypertrophy and transforming growth $factor-{\beta}1\;(TGF-{\beta}1)$ protein levels were evaluated. The glomerular and tubular cells stained positive for $TGF-{\beta}1$ seemed to be more abundant in diabetic SHR than in those with SHR, and GRA treated rats showed somewhat less $TGF-{\beta}1$ protein in glomerular and tubular cells when compared with diabetic SHR. Our results suggest that GRA might be a useful antihypertensive and antidiabetic agent with renoprotective effect.

Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells

  • Kim, Yong-Eun;Kim, Jong Ok;Park, Ki-Sun;Won, Minho;Kim, Kyoon Eon;Kim, Kee K.
    • Molecules and Cells
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    • v.39 no.8
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    • pp.625-630
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    • 2016
  • The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-${\beta}1$ treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-${\beta}1$-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-${\beta}$-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling

  • Kim, Sang-Cheol;Kang, Jung-Il;Hyun, Jin-Won;Kang, Ji-Hoon;Koh, Young-Sang;Kim, Young-Heui;Kim, Ki-Ho;Ko, Ji-Hee;Yoo, Eun-Sook;Kang, Hee-Kyoung
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.417-426
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    • 2017
  • 4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-${\beta}$ (TGF-${\beta}$) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-${\beta}$ signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-${\beta}$-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-${\beta}1$-induced G1/G0 phase arrest and TGF-${\beta}1$-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-${\beta}1$-induced canonical pathway. We observed that ERK phosphorylation by TGF-${\beta}1$ was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-${\beta}1$-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-${\beta}1$-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-${\beta}1$-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-${\beta}1$-induced cell cycle arrest.

The Effects of Platelet-Rich Fibrin on Osteoblast Proliferation and Differentiation: Effects of Platelet-Rich Fibrin on Osteoblasts (혈소판 농축 섬유소가 골모세포 증식과 분화에 미치는 영향)

  • Jung, Hae-Su;Bae, Hyun-Sook;Hong, Ki Seok
    • Journal of dental hygiene science
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    • v.13 no.2
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    • pp.158-164
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    • 2013
  • The most frequently encountered problems at fixture-implantation sites are lack of adequate bone and proximity to anatomic structures. It is generally accepted that growth factors play an essential role in the healing process and tissue formation, and they have become the focus of grafting materials research. The granules in platelets contain high concentrations of various growth factors. In particular, platelet-rich fibrin (PRF) is a second-generation platelet concentrate that allows the production of fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest. This study investigated the in vitro effects of PRF on osteoblasts, in terms of the key cellular functions, and especially the effects on two growth factors, the homodimer of platelet-derived growth factor subunit B (BPDGF-BB) and transforming growth factor (TGF)-${\beta}1$, which are associated with wound healing and regeneration (i.e., proliferation and differentiation). The following parameters were investigated: PDGF-BB and TGF-${\beta}1$ levels in PRF, cell viability, alkaline phosphatase (ALP) activity, type 1 collagen synthesis, and the expressions of osteoblast differentiation markers (ALP and runt-related transcription factor 2) and bone matrix proteins (type 1 collagen). The release of autologous growth factors from PRF was maintained for a reasonable period of time, and exerted positive effects on the proliferation and differentiation of osteoblasts. The use of PRF thus appears to be a promising method for enhancing bone healing and remodeling.