• Title/Summary/Keyword: transforming growth factor

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Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

  • Choi, Hee-Jung;Park, Mi-Ju;Kim, Bo-Sung;Choi, Hee-Jin;Joo, Bosun;Lee, Kyu Sup;Choi, Jung-Hye;Chung, Tae-Wook;Ha, Ki-Tae
    • BMB Reports
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    • v.50 no.8
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    • pp.429-434
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    • 2017
  • Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. $TGF-{\beta}1$ and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of $TGF-{\beta}1$ on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor ${\beta}1$ ($TGF-{\beta}1$) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, $TGF-{\beta}1$ directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of ${\alpha}V$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ via the activation of the $TGF-{\beta}1/TGF-{\beta}RI/Smad2$ signaling pathway. Conversely, the adhesion of $TGF-{\beta}1-stimulated$ endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific $TGF-{\beta}1-mediated$ integrins ${\alpha}V$, ${\beta}1$, and ${\beta}4$ on the endometrial cell membrane. Taken together, these results suggest that $TGF-{\beta}1$ may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

Molecular Signatures of Sinus Node Dysfunction Induce Structural Remodeling in the Right Atrial Tissue

  • Roh, Seung-Young;Kim, Ji Yeon;Cha, Hyo Kyeong;Lim, Hye Young;Park, Youngran;Lee, Kwang-No;Shim, Jaemin;Choi, Jong-Il;Kim, Young-Hoon;Son, Gi Hoon
    • Molecules and Cells
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    • v.43 no.4
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    • pp.408-418
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    • 2020
  • The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

The Effects of Verapamil on Growth and Apoptosis of Keloid Fibroblast (Verapamil이 켈로이드 섬유모세포의 성장과 세포자멸사에 미치는 영향)

  • Park, Jung-Min;Lee, Keun-cheol;Kim, Seok-Kwun;Bae, Hae-Rahn;Rha, Seo-Hee
    • Archives of Plastic Surgery
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    • v.32 no.5
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    • pp.625-635
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    • 2005
  • In this study, the effects of verapamil on growth rate, apoptosis, production of transforming growth factor (TGF-${\beta}$) and fibronectin were evaluated in keloid and normal human dermal fibroblasts. Both fibroblasts were primarily cultured from earlobe keloids of three female patients and treated with various concentrations of verapamil. Cell toxicity was assessed by MTT assay, growth rate and apoptosis by FACS, and the production of TGF-${\beta}$ and fibronectin by ELISA and Western blot, respectively. In the $MTT_{50}$, the cell growth was more suppressed in keloid fibroblasts. In the $MTT_{90}$, cell growth was more stimulated in normal fibroblasts. No significant effect appeared on TGF-${\beta}$ expression but an increase in extracellular fibronectin secretion was found in keloid fibroblasts. Keloid fibroblasts responded to verapamil more sensitively, and the percentage of apoptosis was higher at the $MTT_{50}$l. In brief, verapamil had growth-inhibitory effect with inducing apoptosis at the $MTT_{50}$, but rather growth-stimulatory effect at the $MTT_{90}$. The biphasic effect of verapamil depending on the dose might explain one of the reasons of relapse after keloid treatment with verapamil. Clinical application with high concentration (2.5 mg/ml) is advised unless excessive dosage is used.

QUANTITATIVE ANALYSIS OF TRANSFORMING GROWTH $FACTOR-{\beta}_1$ IN HUMAN FIBROBLASTS INDUCED WITH STAPHYLOCOCCUS ENTEROTOXIN B AND LIPOPOLYSACCHARIDE (Staphylococcus enterotoxin B와 lipopolysaccharide를 작용시킨 사람 섬유아 세포에서 생성된 Transforming Growth $Factor-{\beta}_1$의 정량적 분석)

  • Lee, Seong-Geun;Kim, Kwang-Hyuk;Kim, Uk-Kyu;Kim, Jong-Ryoul;Chung, In-Kyo;Yang, Dong-Kyu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.22 no.2
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    • pp.123-132
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    • 2000
  • $TGF-{\beta}_1$ is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to infection control. The objective of this study is to investigate production of $TGF-{\beta}$ in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of $TGF-{\beta}_1$ which may be responsible for infection control. The fibroblasts were originated from gingiva and facial dermis in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.l{\mu}g$, $1.0{\mu}g$) respectively, $cells(5{\times}10^3ml)$ were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, $cells(2.5{\times}10^5ml)$ were cultivated in EMEM with LPS(0.01, 0.1 and $1.0{\mu}g$), SEB(0.01, 0.1 and $1.0{\mu}g$) respectively and $LPS(0.1{\mu}g)$ and $SEB(0.1{\mu}g)$ in combination for 24, 48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and $TGF-{\beta}_1$ was assayed in duplicate. The results were as follows. 1. In gingival fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell Proliferation occurred very significantly since 3 days after incubation, compared with the control and the production of $TGF-{\beta}_1$ occurred very significantly at 1 day after incubation, compared with the control. 2. In facial dermal fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of $TGF-{\beta}_1$ was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of $TGF-{\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of $TGF-{\beta}_1$ very significantly. The gingival and facial dermal fibroblasts have different phenotype each other The orchestrated understanding of fibroblast proliferation and $TGF-{\beta}_1$ production play an important part in host defense against the bacterial Infection and may prevent tissue necrosis such as necrotizing fasciitis and life-threatening syndrome such as multiple organ failure.

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Korean Red Ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities

  • Choi, Jong Hee;Jang, Minhee;Kim, Eun-Jeong;Lee, Min Jung;Park, Kyoung Sun;Kim, Seung-Hyun;In, Jun-Gyo;Kwak, Yi-Seong;Park, Dae-Hun;Cho, Seung-Sik;Nah, Seung-Yeol;Cho, Ik-Hyun;Bae, Chun-Sik
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.790-798
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    • 2020
  • Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.

Effects of Circular Type TGF-$\beta$1 Antisense Oligonucleotides on Anti-Thy-1 Glomerulonephritis

  • Han, Sang-Mi;Lee, Kwang-Gill;Yeo, Joo-Hong;Kweon, Hae-Yong;Woo, Soon-Ok;Park, Kwan-Kyu
    • Proceedings of the Korean Society of Sericultural Science Conference
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    • 2003.10a
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    • pp.145-146
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    • 2003
  • Overproduction of transforming growth factor (TGF)-$\beta$l has been implicated in the pathogenesis of fibrotic diseases. TGF-$\beta$l plays a crucial role in the accumulation of extracellular matrix (ECM) in human and experimental glomerular diseases. However, it remains unclear whether inhibition of TGF- $\beta$l overproduction would suppress TGF- $\beta$l induced ECM accumulation. To inhibit the overproduction of TGF- $\beta$l in experimental glomerulonephritis induced by anti-Thy 1.1 antibody, we introduced antisense oligodeoxynucleotides (ODN) fur TGF- $\beta$l into the nephritic kidney by the HVJ-liposome-mediated gene transfer method. (omitted)

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대장균내에서 발현된 돼지 TGF-$\beta$1의 분리 및 면역학적 항원성 보유검증

  • Choi, Eun Young;;Kim, Pyung Hyun;Byeon, Woo-Hyeon
    • Microbiology and Biotechnology Letters
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    • v.25 no.2
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    • pp.137-143
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    • 1997
  • Porcine transforming growth factor-$\beta$1 (TGF-$\beta$1) was expressed in Escherichia coli using cDNA of TGF-$\beta$1 and glutathione S-transferase (GST) fusion vector pGEX-1$\lambda$T. An ApoI-Tth111I fragment of cDNA which correspond to the amino acid residues from 123 to 390 of the precursor TGF-$\beta$1 was inserted into EcoRI-Tth111I digested pGEM#-l$\lambda$T and the recombined plasmid was named pGET-12. Gene products from the cloned regions of the recombinant plasmids pGET-12 was not detected in soluble fraction of cell free extract but detected in insoluble fraction. The solubilization of insoluble gene product was achieved by the treatment of N-laurylsarcosine. Molecular weight of partially purified proteins determined by electrophoresis was same as expected from cloned fragment. The ELISA test results of the purified proteins showed that immunologically detectable epitope was preserved in recombinant protein.

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Development of Ginseng yogurt fermented by Bifidobacterium spp (Bifidobacterium을 이용한 인삼 요구르트의 개발)

  • Kim, Na-Young;Han, Myung-Joo
    • Korean journal of food and cookery science
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    • v.21 no.5
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    • pp.575-584
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    • 2005
  • The objective of this study was to develop bioactive ginseng yogurt, fermented by B. minimum KK-1 and B. cholerium KK-2, which showed transforming activity of ginseng extract to compound K. Among older people, 3% ginseng yogurt fermented by B. minimum KK-1 and mixed with Bifidobacterium KK-1, KK-2 showed the highest overall acceptability(6.80, 6.80) among 1%(3.87, 3.67), 2%(4.40, 4.53) and 3% ginseng yogurt. The pH of ginseng yogurt was lower than that of plain yogurt. During 9 days of storage, the pH of each yogurt slightly decreased and then increased until 15 days of storage. The 3 8.25 log CFU/g and B. cholerium KK-2; 7.78 log CFU/g). Therefore, ginseng might be used as a growth factor during the fermentation of yogurt. The L value of ginseng yogurt decreased, and the a and b values increased, with increasing ginseng concentration.

Liver Fibrosis and Five Year Survival of Hepatocellular Cancer Cases Undergoing Transcatheter Arterial Chemo Embolization Using Small Doses

  • Li, Hong;Hu, Yaohong;Li, Na;Zhou, Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1589-1593
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    • 2012
  • Objective: To investigate liver fibrosis, TGF-${\beta}1$ levels and curative effects on hepatocellular carcinoma (HCC) with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE). Methods: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent super-selective transcatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21) chemotherapy groups. Results: With conventional doses, four indices of liver fibrosis focusing on hyaluronate acide (HA), human procollagen type-III (hPC-III), collagen type-Ⅳ (Ⅳ-C) and transforming growth factor-${\beta}l$ (TGF-${\beta}1$) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with small doses there were no significant differences except for TGF-${\beta}1$. Five year survival demonstrated no significant differences between the two groups (P>0.05). Conclusion: To hepatocellular carcinoma patients treated by TACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on five year survival.

Regulation of Pathological Markers during Hepatic Fibrogenesis in Rats

  • Jeong, Won-il;Jeong, Kyu-shik
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2003.10a
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    • pp.16-16
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    • 2003
  • Hepatic fibrosis is a common response to various chronic hepatic injuries and occurs as a consequence of the transformation of hepatic stellate cells into myofibroblasts (MFBs) producing abnormal extracellular matrix which is mainly induced by transforming growth factor-beta (TGF-${\beta}$), especially TGF-${\beta}$1 [1,2]. As the liver becomes fibrotic, there are both quantitative and qualitative changes in several pathological markers related to the hepatic fibrosis. These fibrotic markers in liver are mainly consisted of several proteins and cytokines, but sometimes included specific type cells. The aim of this study was to detect expression and change of markers (TGF-${\beta}$, mallory body, cytokeratin, ${\alpha}$-SMA, hypoxia, collagen) during hepatic fibrogenesis. (omitted)

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