• Title/Summary/Keyword: transforming growth factor

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Characterization and Expression Pattern of the Partial Myostatin cDNA in Shrimp, Fenneropenaeus chinensis

  • Lee, Sang Beum;Kim, Yong Soo;Yoon, Moongeun;Kim, Su-Kyoung;Jang, In Kwon;Lim, Hyun Jeong;Jin, Hyung-Joo
    • Journal of Marine Bioscience and Biotechnology
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    • v.2 no.4
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    • pp.224-229
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    • 2007
  • Muscle tissue expresses many muscle-specific genes, including myostatin (also known as GDF8) that is a member of the transforming growth factor-beta superfamily. Myostatin (MSTN) negatively regulates mammalian skeletal muscle growth and development by inhibiting myoblast proliferation. Mice and cattle possessing mutant MSTN alleles display a 'double muscling' phenotype characterized by extreme skeletal muscle hypertrophy and/or hyperplasia. In this study, we first have characterized partial cDNA of a MSTN gene from the muscle tissue in the F. chinensis and examined its expression pattern in various tissues. The partial MSTN gene (GenBank accession number EU 131093) in the F. chinensis was 1134 bp, encoding for 377 amino acids that showed 63-93% amino acid similarity to other vertebrate MSTNs, containing a conserved proteolytic cleavage site (RXRR) and conserved cysteine residues in the C-terminus. Based on a RT-PCR, the MSTN gene was expressed in the all tissues of F. chinensis used in this study.

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Successful strategy of treatment used to rhBMP-2 and LFA-collagen scaffold for BRONJ (임상가를 위한 특집 3 - rhBMP-2와 LFA-collagen scaffold를 이용한 BRONJ의 성공적인 치료 전략)

  • Kwon, Kyung-Hwan
    • The Journal of the Korean dental association
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    • v.52 no.4
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    • pp.218-233
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    • 2014
  • Bispbosphonates are a class of pharmaceutic agents, which induce apoptosis of osteoclast as well as impair osteoclastic activity to suppress bone resorption. Thus, bisphophonates are effectively used to treat osteoporosis, multiple myeloma and to prevent bone metastases of malignant cancer. However, recently dental disease have been reported associated with Bisphosphonates. Thus, there are a number of discussions about proper prevention and treatment of bisphosphonate-related osteonecrosis of jaw(BRONJ). Marshall R. Urist in 1965 made the seminal discovery that a specific protein, BMP(bone morphogenetic protein), found in the extracellular matrix of demineralized bone could induce bone formation newly when implanted in extraosseous tissues in a host. BMPs are multi-functional growth factors which are members of the transforming growth factor-beta super family and their ability is that plays a pivotal roll in inducing bone. About 18 BMP family members have been identified and characterized. Among of them, BMP-2 and BMP-7 have significant importance in bone development. In this study, patients of BRONJ were recieved who visited Department of oral and maxillofacial surgery, school of dentistry, Wonkwang university for past 3 years from 2011 to 2013. We focused on the results of the surgical intervention. We suggest that new strategy of treatment used to rhBMP-2 and LFA(Lidocaine-Fibrinogen-Aprotinin)-collagen scaffold for patients of BRONJ. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on rhBMP-2 and LFA collage scaffold.

Casein kinase 2 promotes the TGF-β-induced activation of α-tubulin acetyltransferase 1 in fibroblasts cultured on a soft matrix

  • You, Eunae;Jeong, Jangho;Lee, Jieun;Keum, Seula;Hwang, Ye Eun;Choi, Jee-Hye;Rhee, Sangmyung
    • BMB Reports
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    • v.55 no.4
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    • pp.192-197
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    • 2022
  • Cell signals for growth factors depend on the mechanical properties of the extracellular matrix (ECM) surrounding the cells. Microtubule acetylation is involved in the transforming growth factor (TGF)-β-induced myofibroblast differentiation in the soft ECM. However, the mechanism of activation of α-tubulin acetyltransferase 1 (α-TAT1), a major α-tubulin acetyltransferase, in the soft ECM is not well defined. Here, we found that casein kinase 2 (CK2) is required for the TGF-β-induced activation of α-TAT1 that promotes microtubule acetylation in the soft matrix. Genetic mutation and pharmacological inhibition of CK2 catalytic activity specifically reduced microtubule acetylation in the cells cultured on a soft matrix rather than those cultured on a stiff matrix. Immunoprecipitation analysis showed that CK2α, a catalytic subunit of CK2, directly bound to the C-terminal domain of α-TAT1, and this interaction was more prominent in the cells cultured on the soft matrix. Moreover, the substitution of alanine with serine, the 236th amino acid located at the C-terminus, which contains the CK2-binding site of α-TAT1, significantly abrogated the TGF-β-induced microtubule acetylation in the soft matrix, indicating that the successful binding of CK2 and the C-terminus of α-TAT1 led to the phosphorylation of serine at the 236th position of amino acids in α-TAT1 and regulation of its catalytic activity. Taken together, our findings provide novel insights into the molecular mechanisms underlying the TGF-β-induced activation of α-TAT1 in a soft matrix.

Involvement of TGF-β1 Signaling in Cardiomyocyte Differentiation from P19CL6 Cells

  • Lim, Joong-Yeon;Kim, Won Ho;Kim, Joon;Park, Sang Ick
    • Molecules and Cells
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    • v.24 no.3
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    • pp.431-436
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    • 2007
  • Stem cell-based therapy is being considered as an alternative treatment for cardiomyopathy. Hence understanding the basic molecular mechanisms of cardiomyocyte differentiation is important. Besides BMP or Wnt family proteins, $TGF-{\beta}$ family members are thought to play a role in cardiac development and differentiation. Although $TGF-{\beta}$ has been reported to induce cardiac differentiation in embryonic stem cells, the differential role of $TGF-{\beta}$ isoforms has not been elucidated. In this study, employing the DMSO-induced cardiomyocyte differentiation system using P19CL6 mouse embryonic teratocarcinoma stem cells, we investigated the $TGF-{\beta}$-induced signaling pathway in cardiomyocyte differentiation. $TGF-{\beta}1$, but not the other two isoforms of $TGF-{\beta}$, was induced at the mRNA and protein level at an early stage of differentiation, and Smad2 phosphorylation increased in parallel with $TGF-{\beta}1$ induction. Inhibition of $TGF-{\beta}1$ activity with $TGF-{\beta}1$-specific neutralizing antibody reduced cell cycle arrest as well as expression of the CDK inhibitor $p21^{WAF1}$. The antibody also inhibited induction of the cardiac transcription factor Nkx2.5. Taken together, these results suggest that $TGF-{\beta}1$ is involved in cardiomyocyte differentiation by regulating cell cycle progression and cardiac gene expression in an autocrine or paracrine manner.

Hydrogen Peroxide Promotes Epithelial to Mesenchymal Transition and Stemness in Human Malignant Mesothelioma Cells

  • Kim, Myung-Chul;Cui, Feng-Ji;Kim, Yongbaek
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3625-3630
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    • 2013
  • Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by $H_2O_2$ in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with $H_2O_2$, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with $H_2O_2$ promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with $H_2O_2$. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-$1{\alpha}$) and transforming growth factor beta 1 (TGF-${\beta}1$). Considering that treatment with $H_2O_2$ results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.

Analysis of Active Components in Cirsium japonicum var. ussuriense Extracts and Their Effect on TGF-beta Induced Hepatic Stellate Cells Activation (엉겅퀴 추출물의 기능 성분 분석 및 TGF-beta에 의한 간 성상 세포 활성 억제 효과)

  • Kim, Seon-Young;Kim, Sang-Jun;Choi, Young Ji;Yu, Kang-Yeol;Chung, Chang-Ho;Shim, Jae-Suk;Jang, Seon-Il;Yu, Dong-Hyun;Jeong, Seung-Il
    • Korean Journal of Pharmacognosy
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    • v.44 no.2
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    • pp.110-117
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    • 2013
  • Cirsium japonicum (CJ) leaf (L) alcoholic extracts were investigated for analysis their active components (flavonoids and flavanolignans; silymarins) and inhibitory effect on transforming growth factor (TGF)-${\beta}$ induced hepatic stellate cells (HSCs, LX-2 cells) activation. The CJ root (R) extracts were also analyzed and compared with leaf extracts. Total flavonoid and polyphenol contents of the leaf extracts showed higher than those of the root extracts. The content of each flavonoid compound, which was analyzed by HPLC, in CJ-L extracts was also higher than in CJ-R extracts. The results of flavanolignans content in CJ-L and CJ-R extracts were consistent in flavonoid and polyphenol. We studied inhibitory effect of two extracts against TGF-${\beta}1$ induced HSCs activation. The CJ-L extracts significantly suppressed overexpression of profibrogenic factor, ${\alpha}$-smooth muscle actin and collagen-${\alpha}1$(I). The CJ-R extract also showed inhibitory effect on TGF-${\beta}1$ induced HSCs activation, but the efficacy was lower than in CJ-L extract. These results suggest that CJ-L may contribute to the fibrotic liver treatment.

Isolated Cervical Lymph Node Sarcoidosis Presenting in an Asymptomatic Neck Mass: A Case Report

  • Kwon, Yong Shik;Jung, Hye In;Kim, Hyun Jung;Lee, Jin Wook;Choi, Won-Il;Kim, Jin Young;Rho, Byung Hak;Lee, Hye Won;Kwon, Kun Young
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.3
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    • pp.116-119
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    • 2013
  • Sarcoidosis, a systemic granulomatous disease of unknown etiology. The presentation of sarcoidal granuloma in neck nodes without typical manifestations of systemic sarcoidosis is difficult to diagnose. We describe the case of a 37-year-old woman with an increasing mass on the right side of neck. The excisional biopsy from the neck mass showed noncaseating epithelioid cell granuloma of the lymph nodes. No evidence of mycobacterial or fungal infection was noted. Thoracic evaluations did not show enlargement of mediastinal lymph nodes or parenchymal abnormalities. Immunohistochemistry showed abundant expression of tumor necrosis factor-${\alpha}$ in the granuloma. However, transforming growth factor-${\beta}$ was not expressed, although interleukin-$1{\beta}$ was focally expressed. These immunohistochemical findings supported characterization of the granuloma and the diagnosis of sarcoidosis. Sarcoidosis can present with cervical lymph node enlargement without mediastinal or lung abnormality. Immunohistochemistry may support the diagnosis of sarcoidosis and characterization of granuloma.

The Effects of Exercise-based Cardiac Rehabilitation Phase II on Pro- and Anti-inflammatory Markers in Patients with Acute Coronary Syndrome

  • Kim, Al-Chan;Oh, Jae-Keun;Shin, Kyung-Ah;Kim, Young-Joo
    • Biomedical Science Letters
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    • v.19 no.1
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    • pp.61-69
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    • 2013
  • The aim of this study was to evaluate the effect of exercise-based cardiac rehabilitation on pro- and anti-inflammatory markers in patients with acute coronary syndrome (ACS). ACS patients who underwent percutaneous coronary intervention (PCI) and took medicine during phase II of rehabilitation were recruited for study. Subjects were divided into two groups; exercise group (EX, n=21) and a non-exercise group (non-EX, n=13). Supervised exercise program in hospital consisted of treadmill and bicycle exercise was performed three times per week for 6 weeks. Patients of EX received individual counseling, including knowledge of heart disease, risk factor modification, and physical training. Cardiopulmonary fitness, body composition, and biochemical blood factors were analyzed before and after experiment. There was no significant difference in serum levels of hs-CRP and TGF-${\beta}1$ between groups, and between time intervals. But there was a significant decrease in serum levels of IL-18 (P<.001). And there was a significant increase in ratio of IL-18 to IL-10 (P<.01) and serum levels of IL-10 (P<.001). After cardiac rehabilitation, there was significant increase in exercise duration (P<.001), maximal oxygen uptake ($VO_{2peak}$; P<.001) and decrease in submaximal rate-pressure product (sRPP; P<.05) in EX. In conclusion, exercise-based cardiac rehabilitation during phase II in patients with ACS after PCI decreased serum IL-18 (pro-inflammatory) content and ratio of IL-18 to IL-10 in serum (highly related with disease recurrence), and increased serum IL-10 (anti-inflammatory) content. In addition, it led to improved cardiopulmonary fitness.

The Ameliorative Effects of Korean Bean-Leaves on Inflammation and Liver Injury in Obese Rat Model

  • Jin, Byung-Moon;Choi, Seok-Cheol;Lee, Hye-Sook;Jung, Sang-Bong;Hyun, Kyung-Yae
    • Biomedical Science Letters
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    • v.19 no.3
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    • pp.195-205
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    • 2013
  • Obesity may cause metabolic syndrome and adult diseases. This study was undertaken to investigate the ameliorative or useful effects of beanleaves on inflammation and liver damage in obese rat models. Rats were divided into three groups: a control group (normal diet, n=6), a fat diet group (45%-fat diet, n=7), and a bean leaf group (45%-fat+Korean bean leaves diet, n=7). Body weights in the bean leaf group were lower than those of the fat group (P<0.05). Serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$) concentrations were lower in both the control and bean leaf groups than in the fat group (P<0.001). TNF-${\alpha}$ concentrations in the bean leaf group were slightly higher than in the control group but statistically significant (P<0.05). The bean leaf group histologically exhibited lower fatty degeneration, spotty necrosis, and leukocyte infiltrations in hepatic tissues than those of the fat group. In the homogenized liver tissues, the cyclooxygenase-2 (COX-2) gene was only expressed in the fat group. The gene expression levels of hepatic TNF-${\alpha}$, inducible nitric-oxide synthase, peroxiome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), poly (ADP-ribose) polymerase (PARP), and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) were weaker in the bean leaf group than in the fat group. These results suggest that adding bean-leaves to the diet may ameliorate obesity-induced systemic inflammation and liver damage and that bean leaves may be a useful food for preventing obesity and thereby metabolic syndrome and adult diseases.

Comparison of the Sensitivity of Human Bronchial Epithelial Cells to Cigarette Smoke-induced Inflammatory Responses (인간 유래 폐 세포주별 담배연기 분획의 염증 반응 민감도 비교)

  • Yoo, Ji-Hye;Sohn, Hyung-Ok;Park, Chul-Hoon;Lee, Hyeong-Seok;Jang, Mi;Hyun, Hak-Chul;Shin, Han-Jae
    • Journal of the Korean Society of Tobacco Science
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    • v.32 no.1
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    • pp.19-27
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    • 2010
  • The aim of this study is to compare the sensitivity of both two NCI-H292 and A549 cell types to acute inflammatory responses induced by cigarette smoke. For this, we treated two kinds of smoke fractions derived from 2R4F reference cigarettes: total particulate matter(TPM) collected onto a Cambridge filter pad and gas/vapor phase(GVP) prepared by bubbling through in buffer solution. When we measured cellular cytotoxicity by neutral red uptake assay after treatment for 24 hours, TPM and GVP induced cytotoxic effect in a dose-dependent manner in the range of 10-$100{\mu}g$/mL and 60-$300 {\mu}g$/mL., respectively, in both cell types without any cellular difference. Additionally, when we examined acute inflammatory responses by analyzing cytokines secreted into culture media including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-8(IL-8), and transforming growth factor-$\alpha$(TGF-$\alpha$) as well as matrix metalloproteinase-1(MMP-1), the treatment with smoke fractions increased those marker proteins in a dose-dependent manner in NCI-H292. Meanwhile, in A549 cells only MMP-1 was observed to be increased in a dose-dependent fashion. Collectively, our data indicate that NCI-H292 cell type is more sensitive to cigarette smoke-induced inflammatory response than A549 cells. This suggests that NCI-H292 could be useful as an in vitro evaluation tool to assess harmful effects of cigarette smoke.