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Publications (6)22.11 Total impact

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    ABSTRACT: Excessive accumulation of extracellular matrix (ECM) in the kidneys and epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells contributes to the renal fibrosis that is associated with diabetic nephropathy. Histone deacetylase (HDAC) determines the acetylation status of histones and thereby controls the regulation of gene expression. This study examined the effect of HDAC inhibition on renal fibrosis induced by diabetes or transforming growth factor (TGF)-beta1 and determined the role of reactive oxygen species (ROS) as mediators of HDAC activation. In streptozotocin (STZ)-induced diabetic kidneys and TGF-beta1-treated normal rat kidney tubular epithelial cells (NRK52-E), we found that trichostatin A, a nonselective HDAC inhibitor, decreased mRNA and protein expressions of ECM components and prevented EMT. Valproic acid and class I-selective HDAC inhibitor SK-7041 also showed similar effects in NRK52-E cells. Among the six HDACs tested (HDAC-1 through -5 and HDAC-8), HDAC-2 activity significantly increased in the kidneys of STZ-induced diabetic rats and db/db mice and TGF-beta1-treated NRK52-E cells. Levels of mRNA expression of fibronectin and alpha-smooth muscle actin were decreased, whereas E-cadherin mRNA was increased when HDAC-2 was knocked down using RNA interference in NRK52-E cells. Interestingly, hydrogen peroxide increased HDAC-2 activity, and the treatment with an antioxidant, N-acetylcysteine, almost completely reduced TGF-beta1-induced activation of HDAC-2. These findings suggest that HDAC-2 plays an important role in the development of ECM accumulation and EMT in diabetic kidney and that ROS mediate TGF-beta1-induced activation of HDAC-2.
    AJP Renal Physiology 07/2009; 297(3):F729-39. · 4.42 Impact Factor
  • Hunjoo Ha, Eun Y Oh, Hi B Lee
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    ABSTRACT: The 50 kDa glycoprotein plasminogen activator inhibitor 1 (PAI-1) is the major physiological inhibitor of tissue-type and urokinase-type plasminogen activator. These two molecules convert inactive plasminogen into its fibrin-degrading form, plasmin. Plasma and tissue concentrations of PAI-1 are extremely low under normal circumstances but increase under pathologic conditions. This increase is mediated by many factors, including reactive oxygen species. Increased PAI-1 activity is associated with an increased risk of ischemic cardiovascular events and tissue fibrosis. Whereas the antifibrinolytic property of PAI-1 derives mainly from its inhibition of serine proteases, its profibrotic actions seem to derive from a capacity to stimulate interstitial macrophage recruitment and increase transcription of profibrotic genes, as well as from inhibition of serine proteases. Despite studies in mice that lack or overexpress PAI-1, the biological effects of this molecule in humans remain incompletely understood because of the complexity of the PAI-1-plasminogen-activator-plasmin system. The cardioprotective and renoprotective properties of some currently available drugs might be attributable in part to inhibition of PAI-1. The development of an orally active, high-affinity PAI-1 inhibitor will provide a potentially important pharmacological tool for further investigation of the role of PAI-1 and might offer a novel therapeutic strategy in renal and cardiovascular diseases.
    Nature Reviews Nephrology 05/2009; 5(4):203-11. · 7.94 Impact Factor
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    ABSTRACT: The aim of this study was to investigate predictors of adolescence suicidality in a longitudinal study. Additionally, the prevalence of deliberate self-harm behavior and suicide ideation at age 7 and during middle school were examined. Initial assessment data was obtained from 1998 to 2000, and a follow-up assessment was performed in 2006 when the original subjects became middle school students. The addresses and names of 1,857 subjects were located from the original data; they were 910 boys and 947 girls. The subjects were evaluated with the Korean version of the Child Behavior Checklist (K-CBCL), which was administered by the parents of the children, and by various demographic and psychosocial factors. They were reassessed using self reports on the Korea Youth Self Report (K-YSR); in particular, replies to items related to self-harm behavior and suicide ideation were recorded. A logistic regression analysis showed that the factors of gender, economic status, the overall amount of behavior problems, the tendency to internalizing and externalizing problems, somatic problems, thought problems, delinquent behavior, and aggressive behavior were independent predictors of adolescent suicide ideation and self-harm behavior. The importance of total behavior problems suggested that adolescent difficulty is a consequence of an accumulation of various risk factors. Accordingly, clinicians must consider a range of internalizing and externalizing issues, especially overall adaptation, for suicide intervention.
    Journal of Korean medical science 05/2009; 24(2):215-22. · 0.84 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate whether the presence of the NCEP-ATP III defined metabolic syndrome (MS) is associated with the future development of cardiovascular disease (CVD) and diabetes in Koreans. The study subjects were recruited from among those who visited the Health Promotion Center at the Samsung Medical Center. 2435 subjects (1761 men and 674 women), 20 to 78 years of age, were enrolled and evaluated for the development of new onset CVD (coronary heart disease [CHD] and stroke) during a mean 8.7 years of follow-up. The prevalence of the MS at baseline was 21.7% (382/1761) and 11.4% (77/674) in men and women respectively, and the MS was found to be associated with the risk for CVD in both men and women (OR, 1.98; 95% CI, 1.30-3.03 in men, 4.04; 95% CI, 1.78-9.14 in women). More specifically, the MS was associated with the risk for future CHD (OR, 3.68; 95% CI, 1.93-7.01) in men and stroke (OR, 3.96; 95% CI, 1.58-9.94) in women. However, no statistical differences were found between the HOMA-IR tertiles with regard to the risk for CVD. After controlling for fasting plasma glucose (FPG) levels, the predictive power of the MS for an increased risk for diabetes was dramatically decreased (OR, from 3.69 to 1.77) in men, and it no longer was a predictor in women. The NCEP-defined MS was found to be associated with the risk for future CVD, i.e., CHD in men and stroke in women.
    International journal of cardiology 02/2009; 134(3):313-21. · 6.18 Impact Factor
  • Journal of Korean Endocrine Society 01/2006; 21(3).
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    ABSTRACT: Over the past 20 years, allo-transplantation of islet or whole pancreas for reaching and sustaining near-normoglycemia, as close as possible to the physiological model, have been undertaken. As previously known, even though islet transplantation is possible as a safe re-transplant, it is not well known whether re-transplantation of islets is suitable for patients who have lost the grafted islet function. We have performed a human islet allo-transplantation and re-transplantation on an IDDM patient for the first time in Asia and Korea. The recipient was a 32-year-old male and his insulin requirement was 75-85 U per day. After islet transplantation, the basal C-peptide increased from 0.6 to 2.1 ng/ml and insulin requirement decreased from 80 to 36 U per day, indicating that the grafted islets were functional. However, the grafted islets lost function 70 days after the transplantation. So, we performed re-transplantation of the islets. After the re-transplantation, the glucose profile became more stable and frequent episodes of severe hypoglycemia completely disappeared. His severe neuropathic pain improved dramatically and he could engage his ordinary daily life without any antineuropathic drugs. The success of this re-transplantation is one step closer to becoming a viable alternative for the millions of individuals who are suffering from diabetes.
    Diabetes Research and Clinical Practice 06/2002; 56(2):107-13. · 2.74 Impact Factor