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Increased Primary Cilia in Idiopathic Pulmonary Fibrosis
Lee, Junguee,Oh, Dong Hyun,Park, Ki Cheol,Choi, Ji Eun,Kwon, Jong Beom,Lee, Jongho,Park, Kuhn,Sul, Hae Joung Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.3
Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.
Loss of Primary Cilia Results in the Development of Cancer in the Murine Thyroid Gland
Lee, Junguee,Yi, Shinae,Chang, Joon Young,Kim, Jung Tae,Sul, Hae Joung,Park, Ki Cheol,Zhu, Xuguang,Cheng, Sheue-yann,Kero, Jukka,Kim, Joon,Shong, Minho Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.2
Communications at the interface between the apical membrane of follicular cells and the follicular lumen are critical for the homeostasis of thyroid gland. Primary cilia at the apical membrane of thyroid follicular cells may sense follicular luminal environment and regulate follicular homeostasis, although their role in vivo remains to be determined. Here, mice devoid of primary cilia were generated by thyroid follicular epithelial cell-specific deletion of the gene encoding intraflagellar transport protein 88 (Ift88). Thyroid follicular cellspecific Ift88-deficient mice showed normal folliculogenesis and hormonogenesis; however, those older than 7 weeks showed irregularly dilated and destroyed follicles in the thyroid gland. With increasing age, follicular cells with malignant properties showing the characteristic nuclear features of human thyroid carcinomas formed papillary and solid proliferative nodules from degenerated thyroid follicles. Furthermore, malignant tumor cells manifested as tumor emboli in thyroid vessels. These findings suggest that loss-of-function of Ift88/primary cilia results in malignant transformation from degenerated thyroid follicles.
LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease
Lee Jibeom,Kim Hyeonhui,Kang Yun-Won,Kim Yumin,Park Moon-young,Song Ji-Hong,Jo Yunju,Dao Tam,Ryu Dongryeol,Lee Junguee,Oh Chang-Myung,Park Sangkyu 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.
Loss-of-function of IFT88 determines metabolic phenotypes in thyroid cancer
Lee, Junguee,Yi, Shinae,Won, Minho,Song, Young Shin,Yi, Hyon-Seung,Park, Young Joo,Park, Ki Cheol,Kim, Jung Tae,Chang, Joon Young,Lee, Min Joung,Sul, Hae Joung,Choi, Ji Eun,Kim, Koon Soon,Kero, Jukka Nature Publishing Group 2018 Oncogene Vol.37 No.32
Jina Lee,Bong Kyun Kim,Hae Joung Sul,Jong Ok Kim,Junguee Lee,Woo Young Sun 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.5
Purpose: Fine-needle aspiration biopsy (FNAB) can be used to diagnose thyroid cancer and other tumors. Although FNAB without negative pressure (FNAB-P) reduces the risk of blood contamination, FNAB with negative pressure (FNAB+P) increases the sensitivity of the biopsy results. Therefore, we performed a randomized study of FNAB with or without negative pressure to identify the better diagnostic method. Methods: Between March 2016 and February 2017, 172 consecutive patients were enrolled to investigate >0.5 cm nodules with indeterminate or suspicious malignant features. Patients were randomly assigned to the FNAB+P group (a 50 mL syringe was used to provide negative pressure) or to the FNAB-P group (passive collection of blood in the needle’s hub). The 2 methods’ diagnostic adequacy and quality were evaluated using an objective scoring system. The study’s protocol was registered with the World Health Organization Clinical Research Information Service (http://cris.nih.go.kr/cris, KCT0001857). Results: The patients were randomly assigned to the FNAB+P group (n = 86) or the FNAB-P group (n = 86). There were no significant intergroup differences in nodule position, size, age, consistency, calcification, BRAF mutation, or pathology. Evaluation of diagnostic adequacy parameters revealed no significant differences in background blood/clot (P = 0.728), amount of cellular material (P = 0.052), degree of cellular degeneration (P = 0.622), degree of cellular trauma (P = 0.979), or retention of appropriate architecture (P = 0.487). Furthermore, there was no significant intergroup difference in the diagnostic quality (P = 0.634). Conclusion: This prospective randomized study failed to detect significant differences in the diagnostic adequacy and quality of FNAB with or without negative pressure. Therefore, the examiner may select whichever FNAB method they prefer
Kang, Jungue,Lee, Eun-Yong,Song, Bong-Keun,Lee, Seung-Deok,Yook, Tae-Han,Ahn, Seong-Hun,Son, Il-Hong,Kim, Sungchul KOREAN PHARMACOPUNCTURE INSTITUTE 2013 Journal of pharmacopuncture Vol.16 No.2
Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO) extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the $LD_{50}$ of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.
Kim, Dae Hong,Hwang, Jae Sam,Lee, Ik Hwan,Nam, Seung Taek,Hong, Ji,Zhang, Peng,Lu, Li Fang,Lee, Junguee,Seok, Heon,Pothoulakis, Charalabos,Lamont, John Thomas,Kim, Ho American Society for Biochemistry and Molecular Bi 2016 The Journal of biological chemistry Vol.291 No.7
<P>The epithelial cells of the gut form a physical barrier against the luminal contents. The collapse of this barrier causes inflammation, and its therapeutic restoration can protect the gut against inflammation. EGF enhances mucosal barrier function and increases colonocyte proliferation, thereby ameliorating inflammatory responses in the gut. Based on our previous finding that the insect peptide CopA3 promotes neuronal growth, we herein tested whether CopA3 could increase the cell proliferation of colonocytes, enhance mucosal barrier function, and ameliorate gut inflammation. Our results revealed that CopA3 significantly increased epithelial cell proliferation in mouse colonic crypts and also enhanced colonic epithelial barrier function. Moreover, CopA3 treatment ameliorated Clostridium difficile toxin As-induced inflammation responses in the mouse small intestine (acute enteritis) and completely blocked inflammatory responses and subsequent lethality in the dextran sulfate sodium-induced mouse model of chronic colitis. The marked CopA3-induced increase of colonocyte proliferation was found to require rapid protein degradation of p21(Cip1/Waf1), and an in vitro ubiquitination assay revealed that CopA3 directly facilitated ubiquitin ligase activity against p21(Cip1/Waf1). Taken together, our findings indicate that the insect peptide CopA3 prevents gut inflammation by increasing epithelial cell proliferation and mucosal barrier function.</P>
( Yuna Kim ),( Baeki E. Kang ),( Karim Gariani ),( Joanna Gariani ),( Junguee Lee ),( Hyun-jin Kim ),( Chang-woo Lee ),( Kristina Schoonjans ),( Johan Auwerx ),( Dongryeol Ryu ) 생화학분자생물학회 2024 BMB Reports Vol.57 No.2
The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.
β-cell serotonin production is associated with female sex, old age, and diabetes-free condition
Kim, Yeong Gi,Moon, Joon Ho,Kim, Kyuho,Kim, Hyeongseok,Kim, Juok,Jeong, Ji-Seon,Lee, Junguee,Kang, Shinae,Park, Joon Seong,Kim, Hail Academic Press 2017 Biochemical and biophysical research communication Vol. No.
<P><B>Abstract</B></P> <P>Serotonin is known to be present in pancreatic β-cells and to play several physiological roles, including insulin secretion, β-cell proliferation, and paracrine inhibition of α-cells. However, the serotonin production of different cell lines and islets has not been compared based on age, sex, and diabetes related conditions. Here, we directly compared the serotonin concentrations in βTC and MIN6 cell lines, as well as in islets from mice using ultra-performance liquid chromatography tandem mass spectrometry. The average serotonin concentration was 5–10 ng/mg protein in the islets of male and non-pregnant female mice. The serotonin level was higher in females than males at 8 weeks, although there was no difference at 1 year. Furthermore, we observed serotonin by immunofluorescence staining in the pancreatic tissues of mice and human. Serotonin was detected by immunofluorescence staining in a portion of β-cells from islets of old female mice, but not of male or young female mice. A similar pattern was observed in human pancreas as well. In humans, serotonin production in β-cells was associated with a diabetes-free condition. Thus, serotonin production in β-cells was associated with old age, female sex, and diabetes-free condition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Actual serotonin concentrations in cell lines and islets are compared. </LI> <LI> Serotonin over-production in mouse β-cell is aged and female specific. </LI> <LI> Ovariectomy lowers serotonin concentrations in islets. </LI> <LI> Serotonin over-production in human β-cell is aged, female, and non-diabetes specific. </LI> </UL> </P>