• Title/Summary/Keyword: transforming growth factor

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Role of Reactive Oxygen Species in Transforming Growth Factor-β1-inuduced Fibronectin Secretion and α-Smooth Muscle Actin Expression in Human Lung Fibroblasts (사람 폐 섬유아세포의 전환성장인자-β1에 의한 fibronectin 분비와 α-smooth muscle actin 표현에 있어서 활성산소족의 역할)

  • Ha, Hunjoo;Yu, Mi-Ra;Uh, Soo-taek;Park, Choon Sik;Lee, Hi Bahl
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.3
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    • pp.267-276
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    • 2005
  • Background : The transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) plays a key role in lung fibrosis. However, the molecular mechanisms involved in $TGF-{\beta}1$-induced lung fibrosis are unclear. $TGF-{\beta}1$ is the key inducer of myofibroblast transdifferentiation via de novo synthesis of ${\alpha}-smooth$ muscle actin (${\alpha}-SMA$). Since $TGF-{\beta}1$ signals through reactive oxygen species (ROS) and ROS have been shown to induce accumulation of extracellular matrix (ECM) in various tissues, this study examined if ROS play a role in $TGF-{\beta}1$-induced fibronectin secretion and ${\alpha}-SMA$ expression in human lung fibroblasts, MRC-5 cells. Methods : Growth arrested and synchronized MRC-5 cells were stimulated with $TGF-{\beta}1$ (0.2-10 ng/ml) in the presence or absence of N-acetylcysteine (NAC) or diphenyleneiodonium (DPI) for up to 96 hours. Dichlorofluorescein (DCF)-sensitive cellular ROS were measured by FACScan and secreted fibronectin and cellular ${\alpha}-SMA$ by Western blot analysis. Results : $TGF-{\beta}1$ increased the level of fibronectin secretion and ${\alpha}-SMA$ expression in MRC-5 cells in a dosedependent manner. Both NAC (20 and 30 mM) and DPI (1 and $5{\mu}M$) significantly inhibited $TGF-{\beta}1$-induced fibronectin and ${\alpha}-SMA$ upregulation. The $TGF-{\beta}1$-induced cellular ROS level was also significantly reduced by NAC and DPI. Conclusions : The results suggest that NADPH oxidase-dependent ROS play an important role in $TGF-{\beta}1$-induced fibronectin secretion and ${\alpha}-SMA$ expression in MRC-5 cells, which leads to myofibroblast transdifferentiation and progressive lung fibrosis.

Ethanol extract of medicinal herbal mixture accelerates hair growth and melanogenesis in vivo and in vitro (한약재 복합추출물이 모발 성장 및 멜라닌 생성 촉진에 미치는 영향)

  • Kim, Ji Yoon;Kim, Yoo-Jin;Kim, Moon Ju;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.33 no.5
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    • pp.9-18
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    • 2018
  • Objectives : This study was performed to determine the transdermal effects of ethanol extract from medicinal herbal mixture (SHJ) on hair growth in C57BL/6 mice and melanogenesis in melanoma cells. Methods : Mice were divided into 3 experimental groups including vehicle (CON), SHJ extract and 5% minoxidil (MNXD, positive control)-treated group. SHJ was applied topically on the hair-shaved skin of C57BL/6 mice everyday for 15 days. The thickness and density of hair with a folliscope and morphometry of hair follicle with a H&E staining were monitored at last day. Also then, hair growth-associated gene expressions were measured by immunoblot assay. Results : The MNXD or SHJ-treated group promoted on hair growth compared to that of vehicle-treated group (CON). Hair density and thickness of MNXD or SHJ treated-group increased compared to that of vehicle application on the 15 days, respectively. Induction of insulin-like growth factor (IGF)-1 and vascular endothelial growth factor (VEGF) were also accelerated by application of SHJ extract compared to those of CON group. But expression of transforming growth factor (TGF)-${\beta}1$ decreased in SHJ treated-group compared to that of CON group. Furthermore, SHJ extract showed to increase melanin contents in a dose-dependent manner. Tyrosinase activity significantly increased in SHJ-treated group compared with CON group in dose-dependant manner. Conclusions : These results suggest that SHJ can be used as a component of cosmeceuticals for hair care via promoting growth and melanogenesis of hair.

Panax ginseng total protein promotes proliferation and secretion of collagen in NIH/3T3 cells by activating extracellular signal-related kinase pathway

  • Chen, Xuenan;Wang, Manying;Xu, Xiaohao;Liu, Jianzeng;Mei, Bing;Fu, Pingping;Zhao, Daqing;Sun, Liwei
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.411-418
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    • 2017
  • Background: Recently, protein from ginseng was studied and used for the treatment of several kinds of diseases. However, the effect of ginseng total protein (GTP) on proliferation and wound healing in fibroblast cells remains unclear. Methods: In this study, cell viability was analyzed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Cell cycle distribution was analyzed by flow cytometer. The levels of transforming growth factor ${\beta}1$, vascular endothelial growth factor, and collagens were analyzed by enzyme-linked immunosorbent assay and immunofluorescence staining. The expressions of cyclin A, phosphorylation of extracellular signal-related kinase (p-ERK1/2), and ERK1/2 were analyzed by Western blotting. Results: Our results showed that GTP promoted cell proliferation and increased the percentage of cells in S phase through the upregulation of cyclin A in NIH/3T3 cells. We also found that GTP induced the secretion of type I collagen, and promoted the expression of other factors that regulate the synthesis of collagen such as transforming growth factor ${\beta}1$ and vascular endothelial growth factor. In addition, the phosphorylation of ERK1/2 at Thr202/Tyr204 was also increased by GTP. Conclusion: Our studies suggest that GTP promoted proliferation and secretion of collagen in NIH/3T3 cells by activating the ERK signal pathway, which shed light on a potential function of GTP in promoting wound healing.

EFFECT OF PRP (PLATELET RICH PLASMA) ON SINUS BONE GRAFTING IN RABBIT (가토의 상악동 골이식술시 혈소판 농축 혈장(Platelet Rich Plasma)의 골형성 효과)

  • Kim, Yong-Yun;Kwon, Kyung-Hwan;Choi, Moon-Ki;Oh, Sung-Hwan;Min, Seung-Ki
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.27 no.2
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    • pp.140-150
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    • 2005
  • Maxillary sinus lifting procedure and bone grafting are used to reconstruct atrophic maxillae. These procedure are usually followed by the placement of endosseous dental implants. Different materials and techniques can be used for sinus bone grafting. Platelets are known to contain various growth factors involved in the repair of the vasculature and tissues, and it is known that the specialized platelet secretory granules, the alpha granules, contain platelet derived growth factor(PDGF), transforming growth factor-beta(TGF-beta), insuline like growth factor-I(IGF-I), epidermoid growth factor(EGF), and others. This study was to evaluate the effect of PRP on bone formation in a sinus bone grafting. Twelve rabbits were included in this randomized, blinded, prospective pilot study. In experimental group, sinus bone grafting with autobone and platelet rich plasma. In control group, sinus bone grafting with only autobone. Rabbits were sacrificed at 2nd, 4th, 8th, 12th weeks postoperatively. Clinical and radiographic tests, histological analysis were conducted to compare both sides. In clinical examination, there in no significant difference between experimental group and control group. But, in radiographic examination, a distinct incresed in the radiopaque of the PRP experimental group at 2nd and 4th weeks. The histologic examination revealed that more new bone formation and osteoblast activity were seen in experimental group at 2nd and 4th weeks. In conclusion, PRPs action in sinus bone grafting had a capacity of increased new bone formation in a early bone healing stage.

Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review

  • Castro, Fernanda Cavallari de;Cruz, Maria Helena Coelho;Leal, Claudia Lima Verde
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.8
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    • pp.1065-1074
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    • 2016
  • Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-${\beta}$) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.

Effects of Human Capital and Innovation on Economic Growth in Selected ASEAN Countries: Evidence from Panel Regression Approach

  • CHE SULAIMAN, Nor Fatimah;SAPUTRA, Jumadil;MUHAMAD, Suriyani
    • The Journal of Asian Finance, Economics and Business
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    • v.8 no.7
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    • pp.43-54
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    • 2021
  • Human capital and innovation capacities are essential elements and one of the sustainable approaches to driving economic growth. However, there is debate among scholars concerning these two factors in fostering economic growth. This study investigates the relationships between human capital and innovation capacity and economic growth in selected ASEAN countries, namely, Malaysia, Thailand, and Indonesia. Economists widely discussed the interrelation of human capital and innovation. A large body of literature stated that human capital is an essential factor and engine of economic growth. Innovation has become key in transforming the economic development of developing countries. We analyze human capital (HC) and innovation capacity (INC) using static panel data analysis. The data analysis shows that the fixed-effect model is the best model in this study. Further, human capital (HC) has a significant positive relationship with economic growth. Meanwhile, innovation capacity has no significant relationship with economic growth. We also found that Malaysia's coefficient of human capital and innovation capacity is higher and more efficient than in Thailand and Indonesia. In conclusion, human capital and innovation capacity are crucial elements for measuring economic growth. Skilled human capital contributes significantly to the economic growth and economic development of a nation.

Korean Red Ginseng mitigates spinal demyelination in a model of acute multiple sclerosis by downregulating p38 mitogen-activated protein kinase and nuclear factor-κB signaling pathways

  • Lee, Min Jung;Chang, Byung Joon;Oh, Seikwan;Nah, Seung-Yeol;Cho, Ik-Hyun
    • 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.

Transforming Growth Factor Beta-1 C-509T Polymorphism and Cancer Risk: A Meta-analysis of 55 Case-control Studies

  • Liu, Yang;Lin, Xian-Fan;Lin, Chun-Jing;Jin, Si-Si;Wu, Jin-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4683-4688
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    • 2012
  • Aim: To investigate the association of transforming growth factor-beta 1 (TGF-${\beta}1$) C-509T polymorphism and susceptibility to cancer by means of meta-analysis. Methods: An extensive search was performed to identify eligible case-control studies investigating such a link. The strength of the association between TGF-${\beta}1$ C-509T polymorphism and cancer risk was assessed by pooled odds ratios (ORs) and 95%confidence intervals (95%CIs) in fixed or random effects models. Results: 55 published case-control studies with a total number of 21,639 cases and 28,460 controls were included. Overall, there was no association between TGF-${\beta}1$ C-509T and cancer risk in all genetic comparison models (TT vs. CC: OR=1.01, 95%CI=0.89-1.15; T vs. C: OR=1.01, 95%CI=0.94-1.07). However, a stratified analysis by cancer type indicated -509 T allele was significantly associated with decreased risk of colorectal cancer (CRC) (TT vs. CT/CC: OR=0.85, 95%CI=0.76-0.95), especially for Caucasians (TT vs. CT/CC: OR=0.83, 95%CI=0.71-0.98) and for population-based studies (TT vs. CT/CC: OR=0.78, 95%CI=0.68-0.89). Conclusion: This meta-analysis suggested that TGF-${\beta}1$ C-509T polymorphism might contribute to a decreased risk on colorectal cancer susceptibility, especially for Caucasians.

Increased Serum Endoglin and Transforming Growth Factor β1 mRNA Expression and Risk of Hepatocellular Carcinoma in Cirrhotic Egyptian Patients

  • Teama, Salwa;Fawzy, Amal;Teama, Shirin;Helal, Amany;Drwish, Amira Diyaa;Elbaz, Tamer;Desouky, Eman
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.5
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    • pp.2429-2434
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    • 2016
  • Transforming growth factor-B1 ($TGF-{\beta}1$ )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of $ENG/TGF-{\beta}1$ mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and $TGF-{\beta}1$mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of $TGF-{\beta}1$mRNA was 1.4 (0.19 -6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and $TGF-{\beta}1$ mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (P<0.05). Our data suggested that increased ENG and $TGF-{\beta}1$ gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and $TGF-{\beta}1$ as targets for therapy and treatment strategies are warranted.

Epimedium koreanum Nakai Water Extract Regulates Hepatic Stellate Cells Activation through Inhibition of Smad Signaling Pathway (음양곽(淫羊藿) 열수 추출물의 Smad 신호 억제를 통한 간성상세포의 활성 조절)

  • Jung, Ji Yun;Min, Byung-Gu;Park, Chung A;Byun, Sung Hui;Cho, Il Je;Kim, Sang Chan
    • Herbal Formula Science
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    • v.26 no.3
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    • pp.183-193
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    • 2018
  • Objectives : In Traditional Korean Medicine, Epimedium koreanum Nakai has diverse pharmacological activities to treat impotence, forgetfulness, cataract and exophthalmos. Present study investigated anti-fibrogenic effects of E. koreanum water extract (EKE) in hepatic stellate cells (HSCs). Methods : To study anti-fibrogenic effects of EKE, LX-2 cells, a human immortalized HSCs, were pre-treated with $3-300{\mu}g/mL$ of EKE, and then subsequently exposed to 5 ng/mL of transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$). Expression level of ${\alpha}-smooth$ muscle actin was determined by immunoblot analysis. Phosphorylation of Smad, transactivation of Smad, and expression of plasminogen activator inhibitor-1 (PAI-1) were monitored to investigate the effect of EKE on $TGF-{\beta}1-mediated$ signaling pathway. Results : Up to $100{\mu}g/mL$, EKE did not show any cytotoxicity on LX-2 cells. Pre-treatment of EKE ($100{\mu}g/mL$) significantly inhibited ${\alpha}-smooth$ muscle actin expression induced by $TGF-{\beta}1$. In addition, EKE significantly decreased Smad2 and Smad3 phosphorylations, Smad binding element-driven luciferase activity and PAI-1 expression by $TGF-{\beta}1$. Of three flavonoid compounds found in EKE, only quercertin ($30{\mu}M$) attenuated $TGF-{\beta}1-mediated$ PAI-1 expression. Conclusion : These results suggest that EKE has an ability to suppress fibrogenic process in HSCs via inhibition of $TGF-{\beta}1/Smad$ signaling pathway.