• Title/Summary/Keyword: Transforming growth factor-1

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생쥐 난소의 발생단계에 따른 Growth Differentiation Factor-9의 유전자 발현 (Expression of Growth Differentiation Factor-9 in the Mouse Ovaries at Different Developmental Stages)

  • 윤세진;이경아;고정재;차광열
    • 한국발생생물학회지:발생과생식
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    • 제3권1호
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    • pp.95-100
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    • 1999
  • Growth/differentiation factor-9 (GDF-9)은 transforming growth factor $\beta$ (TGF-$\beta$) superfamily의 member로서 난소의 난자에서만 특이적으로 발현되며 정상적인 난포발달에 있어 필수적인 성숙인자로 최근에 알려졌다. 본 연구는 RT-PCR을 통해 생쥐의 원시난포에서의 GDF-9 mRNA의 발현 여부와 함께 난포의 발달단계에 따른 상대적인 발현량을 분석하고자 실시하였다. 본 실험에는 ICR 생쥐를 사용하여 질전 (vaginal plug)이 확인된 날을 1일로 하여 임신 19일의 태아와 태어난 날을 1일로 하여 생후 1일, 10일, 21일, 28일된 생쥐 난소를 실험에 사용하였다. 각 발달단계의 난소조직으로부터 total RNA를 추출하여 GDF-9 유전자 발현 여부를 확인하였으며 이들을 $\beta$-actin에 대해 상대적인 정량분석을 하였다. GDF-9 유전자 발현은 아직은 성장을 시작하지 않은 임신 19일의 태아의 난소, 대부분이 원시난포로 이루어진 태어난 날의 생쥐 난소에서도 확인되었으며, 성장이 왕성하게 진행되고 있는 난포 즉, antrum 형성 이전의 growing follicles이 주를 이루는 생후 10일째의 난소에서 가장 높은 GDF-9 유전자 발현이 관찰되었다. 나머지 단계의 난소에서는 거의 비슷한 정도로 발현함을 관찰할 수 있었다. 본 연구의 결과는 생쥐의 원시난포에도 GDF-9 transcript가 존재한다는 것을 확실하게 증명하였으며, GDF-9이 생쥐의 초기 난포발달에 중요한 역할을 할 것이라는 가능성을 시사한다.

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

  • 정해수;배현숙;홍기석
    • 치위생과학회지
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    • 제13권2호
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    • pp.158-164
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    • 2013
  • 임플란트 식립 시 가장 빈번하게 맞게 되는 문제점으로 임플란트 식립 부위에서의 불충분한 골량과 해부학적 구조에 의한 접근성의 문제를 들 수 있다. 일반적으로 성장 인자들은 치유 과정이나 조직 형성에 있어서 가장 기본적인 필수 요소로 인정되고 있다. 이러한 이유로 골 이식 재료의 효과를 증진시키기 위한 성장 인자들이 최근에 주목을 받고 있다. 혈소판 내 granules에는 높은 농도의 다양한 성장 인자들이 포함되어 있다. 특히, platelet-rich fibrin (PRF)는 2세대 혈소판 농축 인자로 항응고제가 들어있지 않은 상태로 얻을 수가 있고, 혈소판과 많은 성장 인자들이 풍부한 섬유소 막을 포함하고 있다. 이번 연구의 목적은 in vitro 상에서 골아 세포에 대한 PRF의 영향을 알아보고자 하였다. 특히 치유와 재생에 연관된 주요 기능으로써 증식과 분화에 대한 영향을 조사하고자 하였다. 이를 위해서, PRF 내에서 방출되는 성장 인자(platelet-derived growth factor subunit B와 transforming growth factor-${\beta}1$)의 농도, 세포의 생존능력, alkaline phosphatase (ALP) activity, type 1 collagen 합성, 골아 세포의 분화 지표로써 ALP와 Runx2의 발현 정도와 골 기질 단백질로써 type 1 collagen의 발현 정도에 대해서 조사하였다. 이 실험을 통하여 PRF는 치유 시 필요한 타당한 기간 동안에 충분히 자가 성장 인자의 방출을 유지하고 있음을 알 수 있었고, 골아 세포의 증식과 분화에 대해서 긍정적인 효과가 있음을 보여 주였다. 제한적인 실험이지만, 골재생을 위한 PRF의 사용은 골 치유와 골 개조에 있어서 증진 효과를 가져다줄 수 있는 촉망되는 방법 중 하나가 될 수 있을 것이다.

인간자궁내막의 탈락막화 (Decudualization)에 있어서 TGF-$\beta$ (Transforming Growth Factor-$\beta$)의 역할 (Transforming Growth Factor-$\beta$ is a Possible Paracrine Mediator in the Human Endometrial Decidualization)

  • 박동욱;최동순;김미란;황경주;조미영;안성희;민철기;유희석
    • Clinical and Experimental Reproductive Medicine
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    • 제30권1호
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    • pp.65-75
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    • 2003
  • Objectives: To investigate the role of TGF (Transforming growth factor-$\beta$) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. Design: In the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-$\beta$1 are added. Methods: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining are utilized to detect proteins in the tissue. Results: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-$\beta$1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-$\beta$1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4, 325 pg/ml in E2-dominant and 2, 000 pg/ml in P4-dominant condition compare to 150 pg/ml in no hormone. In separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-$\beta$ and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. Conclusion: It is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-$\beta$ and HGF are two possible paracrine mediators in the human endometrial decidualization.

Regulation of Tumor Immune Surveillance and Tumor Immune Subversion by TGF-$\beta$

  • Park, Hae-Young;Wakefield, Lalage M;Mamura, Mizuko
    • IMMUNE NETWORK
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    • 제9권4호
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    • pp.122-126
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    • 2009
  • Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

Long-Term Administration of Sopungsungi-won (SP) Prevents Diabetic Nephropathy in Zucker Diabetic Fatty Rats

  • Kim, Youn-Young;Kang, Kwi-Man;Chung, Sung-Hyun
    • Archives of Pharmacal Research
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    • 제25권6호
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    • pp.917-922
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    • 2002
  • We investigated the long term effects of Sopungsungi-won (SP), a Korean traditional formula used for senile constipation and diabetes mellitus, on the development of diabetic nephropathy (DN) in Zucker diabetic fatty (ZDF) rats. ZDF rats were fed regular laboratory chow mixed with SP or rosiglitazone (RSG) for an 8-week period. Kidney hypertrophy was developed with increasing plasma glucose level, and glomerular hypertrophy was improved by 22% and 45% in SP- and RSG-treated rats, respectively. Urinary glucose and albumin excretions were also significantly lower in SP-treated rats than in ZDF control rats. Activation of the mitogen-activated protein kinase (MAPK)-transforming growth factor ${\beta}1$ (TGF ${\beta}1$)-fibronectin pathway in kidney, responsible for glomerular dysfunction, was markedly blunted by SP treatment in a dose dependent manner. Our findings, for the first time, provide strong evidence that long-term administration of SP formula prevents the development and progression of DN in ZDF rats. Human trials are needed to confirm these experimental results.

세균 독소를 작용시킨 섬유아 세포에서 Transforming Growth Factor-${\beta}_1$의 생성 (PRODUCTION OF TRANSFORMING GROWTH FACTOR-${\beta}_1$ IN HUMAN FIBROBLASTS INDUCED WITH BACTERIAL TOXINS)

  • 이성근;김광혁
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제26권4호
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    • pp.345-354
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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 wound healing. The objective of this study is to investigate production of TGF-${\beta}_1$ 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 wound healing. The fibroblasts were originated from facial dermis and hypertrophic scar in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$) 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 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. 2. In hypertrophic scar fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation did not occur at 1 day after incubation, compared with the control. In SEB and LPS exposure in combination, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. However, the production of TGF-${\beta}_1$ did not occur in SEB and LPS exposure respectively. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of TGF-${\beta}_1$ very significantly and both fibroblasts have different phenotype each other in this regard. This data suggest that the significant production of TGF-${\beta}_1$ may develope abnormal wound healing associated with tissue fibroproliferative disorder, such as hypertrophic scar and keloid formation.

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C57BL/6 마우스에서 모발성장 촉진에 대한 Allium cepa (red)와 Angelica gigas Nakai의 효과 (Effect of Allium cepa (red) and Angelica gigas Nakai on Hair-growth Promotion in C57BL/6 Mice)

  • 이진영;동재경;강재선
    • 생명과학회지
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    • 제30권11호
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    • pp.990-998
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    • 2020
  • 본 연구는 C57BL/6 마우스에서 Allium cepa (red) 생물전환 추출물과 Angelica gigas Nakai 추출물이 혼합된 새로운 물질의 모발 성장 촉진 효과를 평가하기 위해 수행되었다. 적양파의 에탄올 추출물을 Bacillus subtilis KJ-3(BS3) 균주의 사용을 통해 생물전환하였고 이것을 Red-BCQ라고 명명하였다. Red-BCQ의 퀘르세틴 함량은 생물전환 후 약 7.4배 증가 되었다. 참당귀 추출물(Agnex)에는 decursin (D), decursinol angelate (DA) 등 쿠마린이 다량 함유되어 있다. Agnex 1 mg 중에는 D 0.4146 mg, DA 0.3659 mg이 포함되어 있었다. 미녹시딜(minoxidil)은 모발 성장을 촉진하는 것으로 알려져 있다. 본 연구에서는 Red-BCQ, Agnex 및 이들 혼합물의 모발 성장 촉진효과를 5% 미녹시딜과 비교하였다. 25마리의 마우스는 생리식염수(CON), 5% 미녹시딜(PCON), Red-BCQ (RA), Agnex (AG), 이들 혼합물 (RAG) 처리군 등 5개의 실험군으로 나누었다. 시료는 하루에 한 번 4주 동안 정해진 시간에 경구로 투여되었다. 모발 증식은 7, 14, 21, 28일에 사진으로 관찰하였다. 또한 5α-reductase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), insulin-like growth factor (IGF)-1, transforming growth factor(TGF)-β1, 항산화효소활성, 피부조직의 모낭도 관찰했다. 모든 결과에서 혼합물 투여 그룹은 다른 그룹보다 항산화 효과와 모발 성장 촉진 효과가 더 컸다. 이러한 데이터는 RAG가 C57BL/6 종의 모발 성장에 대해 강력한 자극활동을 가지고 있음을 시사한다.

TGF-$\alpha$, -$\beta$$_1$, and bFGF mRNA Expression of Lens Epithelial Cells in Senile and Diabetic Cataract

  • Hwang, Bum-Noon;Her, Jun
    • 대한의생명과학회지
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    • 제8권3호
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    • pp.127-135
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    • 2002
  • Anterior subcapsular cataract was developed by opacification with transdifferentiation and abnormal proliferation of lens epithelial cells (LECs) and pathological accumulation of extracellular matrix (ECM). After-cataract also be caused by a similar transdifferentiation of LECs remaining after surgery and the accompanying increase of ECM deposits. It is blown that prostaglandin E2 and cytokine, such as TGF-$\beta$, bFGF, and IL-1, were associated with abnormal proliferation and transdifferentiation of LECs. The aim of this study was to detect the expression of transforming growth factor-$\alpha$ (TGF-$\alpha$), transforming growth factor-$\beta_1$(TGF-$\beta_1$) and basic fibroblast growth factor (bFGF) in LECs of senile and diabetic cataract. The expressions of these growth factors in lens epithelial cells were determined. The sample for growth factor determination were collected in senile cataract patients without metabolic disorder, especially diabetes mellitus and diabetic cataract patients. The mRNA expression of growth factors was detected by semi-quantitative reverse transcription - polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Statistics were analysed using Wilcoxon rank sum test. Semi-quantitative RT-PCR/southern analysis of RNA obtained from thirty surgical specimens demonstrated that the level of mRNA expression of TGF-$\alpha$, -$\beta_1$ and bFGF was increased in diabetic cataract lens tissues compared with senile cataract specimens but non-significant, bFGF and TGF-$\beta_1$ mRNA expression were detected in most patients, expression level of TGF-$\beta_1$ was most high on the basis of normal ocular concentration. Detection rate of TGF-$\alpha$ in diabetic cataract was 1.5 fold higher than in senile cataract (P=0.098). TGF-$\alpha$, TGF-$\beta_1$, and bFGF mRNA expression of LECs were detected in senile and diabetic cataract. In both patient groups, expression level of TGF-$\beta_1$, mRNA was high, so We suggest TGF-$\beta_1$ strong influence in development of senile cataract and of diabetic cataract also. TGF-$\alpha$ expression level was similar but more frequently detected in diabetic cataract than in senile cataract. In conclusion, TGF-$\alpha$ may be associated with early development of diabetic cataract.

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