• Title/Summary/Keyword: TGF-${\beta}3$

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Protective effects of remifentanil against H2O2-induced oxidative stress in human osteoblasts

  • Yoon, Ji-Young;Kim, Do-Wan;Kim, Eun-Jung;Park, Bong-Soo;Yoon, Ji-Uk;Kim, Hyung-Joon;Park, Jeong-Hoon
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.16 no.4
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    • pp.263-271
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    • 2016
  • Background: Bone injury is common in many clinical situations, such as surgery or trauma. During surgery, excessive reactive oxygen species (ROS) production decreases the quality and quantity of osteoblasts. Remifentanil decreases ROS production, reducing oxidative stress and the inflammatory response. We investigated remifentanil's protective effects against $H_2O_2$-induced oxidative stress in osteoblasts. Methods: To investigate the effect of remifentanil on human fetal osteoblast (hFOB) cells, the cells were incubated with 1 ng/ml of remifentanil for 2 h before exposure to $H_2O_2$. For induction of oxidative stress, hFOB cells were then treated with $200{\mu}M$ $H_2O_2$ for 2 h. To evaluate the effect on autophagy, a separate group of cells were incubated with 1 mM 3-methyladenine (3-MA) before treatment with remifentanil and $H_2O_2$. Cell viability and apoptotic cell death were determined via MTT assay and Hoechst staining, respectively. Mineralized matrix formation was visualized using alizarin red S staining. Western blot analysis was used to determine the expression levels of bone-related genes. Results: Cell viability and mineralized matrix formation increased on remifentanil pretreatment before exposure to $H_2O_2$-induced oxidative stress. As determined via western blot analysis, remifentanil pretreatment increased the expression of bone-related genes (Col I, BMP-2, osterix, and $TGF-{\beta}$). However, pretreatment with 3-MA before exposure to remifentanil and $H_2O_2$ inhibited remifentanil's protective effects on hFOB cells during oxidative stress. Conclusions: We showed that remifentanil prevents oxidative damage in hFOB cells via a mechanism that may be highly related to autophagy. Further clinical studies are required to investigate its potential as a therapeutic agent.

The TGFβ→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1

  • Min-Kyu Kim;Sang-Hyun Han;Tae-Geun Park;Soo-Hyun Song;Ja-Youl Lee;You-Soub Lee;Seo-Yeong Yoo;Xin-Zi Chi;Eung-Gook Kim;Ju-Won Jang;Dae Sik Lim;Andre J. van Wijnen;Jung-Won Lee;Suk-Chul Bae
    • Molecules and Cells
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    • v.46 no.10
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    • pp.592-610
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    • 2023
  • The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

Interferon-gamma susceptibility of HL-60 cells, mononuclear cells of umbilical cord blood and bone marrow (HL-60 세포주, 제대혈 및 골수 단핵구 세포의 interferon-gamma에 대한 감수성에 관한 연구)

  • Cheong, Hee Jeong;Hong, Dae Sik;Kim, Sook Ja;Cheong, Jae Hwa;Lee, Joo Young;Lee, Nam Su;Park, Sung Kyu;Won, Jong Ho;Park, Hee Sook;Kim, Sung Il
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.230-235
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    • 2001
  • Background: Finding of the regulation of various gene expression by cytokine including $IFN-{\gamma}$ in hematopoietic stem cell will light up the understanding of pathogenesis of aplastic anemia in various aspects. To study on aplastic anemia, however, we have to circumvent the difficulty of directly obtaining bone marrow stem cells from the patient. Therefore, we tried to find out a cell can replace the bone marrow stem cells for study on cell signaling pathway and regulation of gene expression by $IFN-{\gamma}$. Materials and Methods: HL-60 cells, of 20 ng/mL of $IFN-{\gamma}$. Total RNA was isolated from the cells and RT-PCR of the indoleamine 2,3-dioxygenase (IDO), $IFN-{\gamma}$, TNF-${\alpha}$, $MIP-1{\alpha}$, and $TGF-{\beta}2$ was carried out for the estimation of the gene expression. Results: $IFN-{\gamma}$ induced IDO gene expression of mononuclear cells from umbilical cord blood showed similar pattern as compared to that of bone marrow. Whether $INF-{\gamma}$ was treated or not, $TNF-{\alpha}$ was expressed in both mononuclear cells from umbilical cord blood and bone marrow. However, HL-60 cells showed different expression patterns. HL-60 cells would express neither IDO nor $TNF-{\alpha}$ even under the culture with 20ng/mL of $IFN-{\gamma}$. Conclusion: Our results showed bone marrow can be replaced with mononuclear cells from umbilical cord blood in the study on the relation between aplastic anemia and $IFN-{\gamma}$ including $IFN-{\gamma}$ cell signaling pathway.

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Antioxidant Ability and Hair Growth Effect of Samhwang-Sasimtang in C57BL/6 Model (삼황사심탕의 항산화능 및 C57BL/6 마우스 모델에서의 발모 촉진효과)

  • Kim, Min Ji;Park, Kyo Hyun;Lee, In Chul;Kim, Bae Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.2
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    • pp.154-161
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    • 2014
  • The purpose of this study is to evaluate the antioxidant activity and hair growth effects of a natural herbal ethanol extract, Samhwang-Sasimtang(SS). In case of antioxidant ability of SS, the content of phenolic compounds was 28.44mg/g. The extract showed strong electron donating ability and free radical scavenging activity in a concentration-dependent manner. SOD-like activity also rose through increasing the concentrations of SS. In order to estimate the hair growth effects, the extract was applied to the back of seven-week-old C57BL/6 male mice ($150{\mu}{\ell}$ a day, five days a week, for four weeks) in four groups (C, control, saline; PC, positive control, 3% minoxidil; E1, experimental 1, 1% SS; E2, experimental 2, 2% SS). Ten mice were assigned to each group and five mice in each group were sacrificed at weeks 2 and 4, respectively. There was no a significant difference in body weight change among experimental groups. In macroscopic observation of hair growth at week 4, the scores of hair growth on the backs of mice were 80, 60, 40 and 20% in the PC, E2, E1 and C groups. In terms of histological observation, the ratio and thickness of hair follicles, the enzyme activities of ALP and ${\gamma}$-GT, immunohistological examination of IGF-1 and VEGF which are the hair growth factors, in each group were significantly high in this order: PC, E2, E1 and C group, at week 4. Meanwhile, hair growth inhibition factors, TGF-${\beta}1$ and Caspase-3, were reduced in PC, E1 and E2 groups compared with C group. These results indicate that SS extract may be effective in promoting hair growth, and suggest that it can be used practically as a superior natural agent for hair growth promotion.

Use of Real-Time Quantitative PCR to Identify High Expressed Genes in Head and Neck Squamous Cell Carcinoma Cell Lines

  • Lee, Yong-Gyoo;Chun, So-Young;Lee, Hae-Ahm;Sohn, Yoon-Kyung;Kang, Ku-Seong;Kim, Joung-Ok;Yun, Sang-Mo;Kim, Jung-Wan;Jang, Hyun-Jung
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.1
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    • pp.69-75
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    • 2006
  • Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer among men in the developed world affecting the tongue, pharynx, larynx and oral cavity. HNSCC is thought to represent a multistep process whereby carcinogen exposure leads to genetic instability in the tissue and accumulation of specific genetic events, which result in dysregulation of proliferation, differentiation, and cell loss and the acquisition of invasive capacity. Despite therapeutic and diagnostic progress in oncology during the past decades, the prognosis of HNSCC remains poor. Thus it seems that finding a biological tumor markers which will increase the early diagnosis and treatment monitoring rates, is of paramount importance in respect to improving prognosis. In an effort to identify gene expression signatures that may serve as biomarkers, this study several genes were selected, such as H3,3A, S100A7, UCHL1, GSTP1, PAI-2, PLK, TGF${\beta}$1 and bFGF, and used 7 HNSCC cell lines that were established various anatomical sites, and also 17 other cancer cell lines were used for control group using real-time quantitative RT-PCR and immunocytochemical analysis with a monoclonal antibody. In this study, S100A7 showed a clearly restricted occurrence in tongue originated cell line, and GSTP1 expression level in the pharynx originated cell line was very increased, relative to corresponding other cell lines. These results suggest that S100A7 and GSTP1 genes' expression can occur during tongue and pharynx originated head and neck tumorigenesis and that genetic change is an important driving force in the carcinogenesis process. This data indicate that S100A7 and GSTP1 expression pattern in HNSCC reflect both diagnostic clue and biological marker. And this is provides a foundation for the development of site-specific diagnostic strategies and treatments for HNSCC.

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.

Intronic Polymorphisms of the SMAD7 Gene in Association with Colorectal Cancer

  • Damavand, Behzad;Derakhshani, Shaghayegh;Saeedi, Nastaran;Mohebbi, Seyed Reza;Milanizadeh, Saman;Azimzadeh, Pedram;Aghdaie, Hamid Asadzadeh;Zali, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.41-44
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    • 2015
  • Based on genome-wide association studies (GWAS) a linkage between several variants such as single nucleotide polymorphisms (SNPs) in intron 3 of SMAD7 (mothers against decapentaplegic homolog7) were, rs12953717, rs4464148 and rs4939827 has been noted for susceptibility to colorectal cancer (CRC). In this study we investigated the relationship of rs12953717 and rs4464148 with risk of CRC among 487 Iranian individuals based on a case-control study. Genotyping of SNPs was performed by PCR-RFLP and for confirming the outcomes, 10% of genotyping cases were sequenced with RFLP. Comparing the case and control group, we have found significant association between the rs4464148 SNP and lower risk of CRC. The AG genotype showed decreased risk with and odds ratio of 0.635 (adjusted OR=0.635, 95% CI: 0.417-0.967, p=0.034). There was no significant difference in the distribution of SMAD7 gene rs12953717 TT genotype between two groups of the population evaluated (adjusted OR=1.604, 95% CI: 0.978-2.633, p=0.061). On the other hand, rs12953717 T allele showed a statistically significant association with CRC risk (adjusted OR=1.339, 95% CI: 1.017-1.764, p=0.037). In conclusion, we found a significant association between CRC risk and the rs4464148 AG genotype. Furthermore, the rs12953717 T allele may act as a risk factor. This association may be caused by alternative splicing of pre mRNA. Although we observed a strong association with rs4464148 GG genotype in affected women, we did not detect the same association in CRC male patients.

Variants of Inflammnation-related Genes and the Risk of Gallstones and Biliary Tract Cancer: A population-baged Study in China

  • Hsing, Ann W.;Sakoda, Lori;Chen, Jin-Bo;Rashid, Asif;Wang, Bin-Shen;Shen, Ming-Chang;Chen, Eric;Rosenberg, Phillip;Zhang, Mingdong;Andreotti, Gabriella;Welch, Robert;Yeager, Meredith;Fraumeni Jr. Joseph F.;Gao, Yu-Tang;Stephen J. Chanock
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2006.11a
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    • pp.32-33
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    • 2006
  • There is compelling evidence that chronic inflammation predisposes to biliary tract cancer. Previously we found that aspirin use and variants in the PTGS2 gene, both of which are closely linked to inflammation, were associated with biliary tract cancer risk in a population-based study in China. To test the inflammation hypothesis further, we examined the associations of variants in 20 genes involved in the inflammation pathway with risk of biliary tract cancer and stones in a large population-based case-control study in Shanghai, China. We genotyped 56 single nucleotide polymorphisms (SNPs)from 20 inflammation genes in 411 biliary tract cancer cases (237 gallbladder cancers, 127 extrahepatic bile duct cancers, and 47 ampullary cancers), 895 subjects with biliary stones, and 786 population controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cls) for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer risk. Of the 56 SNPs examined, 20 showed some associations with biliary cancer and stones. Specifically, variants of the IL8, IL8RB, RNASEL, TGF-beta, and TNF-alpha genes were associated with gallstone risk, while variants in the IL1A, IL10, VEGF, and RNASEL genes were associated with gallbladder cancer risk. Adjustment for multiple comparisons did not materially change these results. Of the 10 genes with multiple SNPs, we inferred halotypes; only one haplotype in the IL8RBgene was associated with gallstones. The haplotype frequency was significantly different between bile dict cancer cases and control (p=0.007). A haplotype comprising 3 SNPs in the IL8RB gene (rs2230054, rs1126579, rs1126580) was associated with a 54% increased risk of bile duct stones (95% CI 1.14-2.07, p=0.02), relative to the most frequent haplotype. In summary, common variants in immune-related genes influencing inflammatory responeses were associated with gallstones and biliary tract cancer, lending further support to the role of inflammation in the pathogenesis of biliary stones and biliary tract cancer. Future larger studies with more complete gene coverage are needed to confirm these results.

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The Therapeutic Effect of Angiotensin II Receptor Antagonist in Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증 환자의 치료에서 Angiotensin II Receptor Antagonist의 치료효과)

  • Woo, Duck Soo;Seol, Won Jong;Kyung, Sun Young;Lim, Young Hee;An, Chang Hyeok;Park, Jeong Woong;Jeong, Sung Hwan;Lee, Jae Woong
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.5
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    • pp.478-487
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    • 2003
  • Background : There have been several studies showing that the angiotensin II and angiotensin converting enzyme(ACE) contributes to the apoptosis of alveolar epithelial cells in idiopathic interstitial pneumonia and the activation of fibroblasts during the process of pulmonary fibrosis. These results suggest that the pulmonary fibrosis can be inhibited by the angiotensin II receptor antagonist(AGIIRA). This study was performed to identify the therapeutic effect of AGIIRA in idiopathic pulmonary fibrosis(IPF). Method : Thirteen patients with IPF, who were diagnosed with an open lung biopsy(6 patients) and furfilling the ATS criteria(7 patients) between March 1999 and October 2001 at the Gachon medical center, were enrolled in this study. Of these patients, eight patients were treated with a regimen including AGIIRA(AT group), and five were treated without AGIIRA(NT group). The pulmonary function tests and dyspnea(ATS scale) were measured at diagnosis and 1 year after treatment. All the data was collected to analyze the therapeutic effect of AGIIRA on the patients with IPF. Results : The AT group contained 8 patients(M:F=4:4) and the NT group contained 5 patients(M:F=3:2). There was no significant difference in the serum angiotensin II level between the two groups($202.5{\pm}58.5$ vs $163.7{\pm}47.3pg/ml$, p>0.05). The AT group showed an upward trend in TLC(+3%), FVC(+4%), FEV1(+3%) and DLco(+2%) compared to the NT group(TLC(-14%), FVC(-3%), FEV1(-4%) except for DLco(+5%)). The dyspnea score in the AT group improved significantly but not in the NT group. Conclusion : These results suggest that the angiotensin II receptor antagonist may have an effect on stabilizing IPF.

A Study on the Morphological Structure of Sasul-Sijo (사설시조의 형태구조 연구)

  • Won, Yong-Moon
    • Sijohaknonchong
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    • v.23
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    • pp.161-188
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    • 2005
  • The purpose of this study was to delve into the morphological types of Sijo in an effort to determine the morphological structure of Sasul-sijo, and it's also attempted to present standard about how to discriminate Pyong-si, Eos-sijo and Sasul-sijo from one another from a morphological standpoint. It's suggested that Si with tee Jangs, six verses and 12 stanzas or more, with three Jangs, seven verses and 14 stanzas or more, and with three Jangs, eight verses and 16 stanzas or more should respectively be called Pyong-sijo, Eos-sijo and Sasul-sijo. After what Sijo was and what's not were discussed, how to distinguish Eos-sijo from Sasul-sijo was described, and finally, the structure of Sasul-sijo was presented. As for Sijo and non-Sijo, the types of works that consisted of tee Jangs, like Sijo, yet didn't suit its framework and Yuljo and were written in Chinese characters were regarded as non-Sijo. Concerning discrimination between Eos-si and Sasul-sijo, the type of Sijo that included one more or higher number of verse(s) and two more or higher number of stanzas in one of three Jangs was defined as Eos-sijo, and the type of Sijo that involved two more or higher number of verses and four more or higher number of stanzas in one of three Jangs was called Sasul-sijo. In other words, Eos-sijo contained one more verse in one of tee Jangs, and Sasul-sijo included one more Jang in one tee Jangs. The sort of Sijo that contained one more Jang in one of three Jangs could be viewed as Sasul-sijo. Regarding the structure of Sasul-si, there should be three Jangs, eight verses and 16 stanzas in one piece of Sasul-sijo. Any type of Sijo that contained two more or higher number of verses and four more or higher number of stanzas could be called Sasul-sijo. Such an addition of verse and stanza could done in various ways. The examples were (1) adding stanzas the first Jang, 2) adding stanzas to the second Jang, (3) adding stanzas to the final Jang, (4) adding stanzas to both the first and Second Jangs, (5) adding stanzas to th the second and final Jangs, and (6) adding stanzas to all the first, second and third Jangs at the same time. Besides, there was an extremely broad gap between the numbers of verse and stanza in Sasul-sijo, which ranged from a low of eight stanzas to a high of 87 ones in one of three Jangs.

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