• Title/Summary/Keyword: MEF2D

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MiR-183-5p induced by saturated fatty acids regulates the myogenic differentiation by directly targeting FHL1 in C2C12 myoblasts

  • Nguyen, Mai Thi;Min, Kyung-Ho;Lee, Wan
    • BMB Reports
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    • v.53 no.11
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    • pp.605-610
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    • 2020
  • Skeletal myogenesis is a complex process that is finely regulated by myogenic transcription factors. Recent studies have shown that saturated fatty acids (SFA) can suppress the activation of myogenic transcription factors and impair the myogenic differentiation of progenitor cells. Despite the increasing evidence of the roles of miRNAs in myogenesis, the targets and myogenic regulatory mechanisms of miRNAs are largely unknown, particularly when myogenesis is dysregulated by SFA deposition. This study examined the implications of SFA-induced miR-183-5p on the myogenic differentiation in C2C12 myoblasts. Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. The knockdown of FHL1 by siRNA inhibited myogenic differentiation of myoblasts. Interestingly, miR-183-5p inversely regulated the expression of FHL1, a crucial regulator of skeletal myogenesis, by targeting the 3'UTR of FHL1 mRNA. Furthermore, the transfection of miR-183-5p mimic suppressed the expression of MyoD, MyoG, MEF2C, and MyHC, and impaired the differentiation and myotube formation of myoblasts. Overall, this study highlights the role of miR-183-5p in myogenic differentiation through FHL1 repression and suggests a novel miRNA-mediated mechanism for myogenesis in a background of obesity.

Skill Assessments for Evaluating the Performance of the Hydrodynamic Model (해수유동모델 검증을 위한 오차평가방법 비교 연구)

  • Kim, Tae-Yun;Yoon, Han-Sam
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.14 no.2
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    • pp.107-113
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    • 2011
  • To evaluate the performance of the hydrodynamic model, we introduced 10 skill assessments that are assorted by two groups: quantitative skill assessments (Absolute Average Error or AAE, Root Mean Squared Error or RMSE, Relative Absolute Average Error or RAAE, Percentage Model Error or PME) and qualitative skill assessments (Correlation Coefficient or CC, Reliability Index or RI, Index of Agreement or IA, Modeling Efficiency or MEF, Cost Function or CF, Coefficient of Residual Mass or CRM). These skill assessments were applied and calculated to evaluate the hydrodynamic modeling at one of Florida estuaries for water level, current, and salinity as comparing measured and simulated values. We found that AAE, RMSE, RAAE, CC, IA, MEF, CF, and CRM are suitable for the error assessment of water level and current, and AAE, RMSE, RAAE, PME, CC, RI, IA, CF, and CRM are good at the salinity error assessment. Quantitative and qualitative skill assessments showed the similar trend in terms of the classification for good and bad performance of model. Furthermore, this paper suggested the criteria of the "good" model performance for water level, current, and salinity. The criteria are RAAE < 10%, CC > 0.95, IA > 0.98, MEF > 0.93, CF < 0.21 for water level, RAAE < 20%, CC > 0.7, IA > 0.8, MEF > 0.5, CF < 0.5 for current, and RAAE < 10%, PME < 10%, CC > 0.9, RI < 1.15, CF < 0.1 for salinity.

Acceleration of Mesenchymal-to-Epithelial Transition (MET) during Direct Reprogramming Using Natural Compounds

  • Seo, Ji-Hye;Jang, Si Won;Jeon, Young-Joo;Eun, So Young;Hong, Yean Ju;Do, Jeong Tae;Chae, Jung-il;Choi, Hyun Woo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.10
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    • pp.1245-1252
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    • 2022
  • Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2+/+/ROSA26+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

HDAC11 Inhibits Myoblast Differentiation through Repression of MyoD-Dependent Transcription

  • Byun, Sang Kyung;An, Tae Hyeon;Son, Min Jeong;Lee, Da Som;Kang, Hyun Sup;Lee, Eun-Woo;Han, Baek Soo;Kim, Won Kon;Bae, Kwang-Hee;Oh, Kyoung-Jin;Lee, Sang Chul
    • Molecules and Cells
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    • v.40 no.9
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    • pp.667-676
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    • 2017
  • Abnormal differentiation of muscle is closely associated with aging (sarcopenia) and diseases such as cancer and type II diabetes. Thus, understanding the mechanisms that regulate muscle differentiation will be useful in the treatment and prevention of these conditions. Protein lysine acetylation and methylation are major post-translational modification mechanisms that regulate key cellular processes. In this study, to elucidate the relationship between myogenic differentiation and protein lysine acetylation/methylation, we performed a PCR array of enzymes related to protein lysine acetylation/methylation during C2C12 myoblast differentiation. Our results indicated that the expression pattern of HDAC11 was substantially increased during myoblast differentiation. Furthermore, ectopic expression of HDAC11 completely inhibited myoblast differentiation, concomitant with reduced expression of key myogenic transcription factors. However, the catalytically inactive mutant of HDAC11 (H142/143A) did not impede myoblast differentiation. In addition, wild-type HDAC11, but not the inactive HDAC11 mutant, suppressed MyoD-induced promoter activities of MEF2C and MYOG (Myogenin), and reduced histone acetylation near the E-boxes, the MyoD binding site, of the MEF2C and MYOG promoters. Collectively, our results indicate that HDAC11 would suppress myoblast differentiation via regulation of MyoD-dependent transcription. These findings suggest that HDAC11 is a novel critical target for controlling myoblast differentiation.

Genetics of Alzheimer's Disease

  • Kim, Jong Hun
    • Dementia and Neurocognitive Disorders
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    • v.17 no.4
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    • pp.131-136
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    • 2018
  • Alzheimer's disease (AD) related genes have been elucidated by advanced genetic techniques. Familial autosomal dominant AD genes founded by linkage analyses are APP, PSEN1, PSEN2, ABCA7, and SORL1. Genome-wide association studies have found risk genes such as ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-HLA-DRB1, INPP5D, MEF2C, MS4A6A/MS4A4E, NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1. ABCA7, SORL1, TREM2, and APOE are proved to have high odds ratio (>2) in risk of AD using next generation sequencing studies. Thanks to the promising genetic techniques such as CRISPR-CAS9 and single-cell RNA sequencing opened a new era in genetics. CRISPR-CAS9 can directly link genetic knowledge to future treatment. Single-cell RNA sequencing are providing useful information on cell biology and pathogenesis of diverse diseases.

Effects of polysaccharide (polycan) derived from black yeast in dexamethasone-induced muscle atrophy cell model (Dexamethasone으로 유도한 근위축 세포모델에서 흑효모 배양물 유래 polycan의 근위축 개선에 대한 효과)

  • Hwang, Su-Jin;Lim, Jong-Min;Ku, Bon-Hwa;Cheon, Da-Mi;Jung, Yu Jin;Kim, Young-Suk;Oh, Tae Woo
    • Herbal Formula Science
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    • v.29 no.1
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    • pp.45-55
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    • 2021
  • Objectives : This study was conducted to evaluate the anti-atrophic effect of polycan in dexamethasone-induced skeletal muscle atrophy in vitro model. Methods : C2C12 myoblast were differentiated into myotube by 2% horese serum medium for 6 days, and then treated polycan extract at different concentrations for 24h. The effect of dexamethasone on the induction of muscle atrophy and expression of atrophy-related genes in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : The results showed that Treatment with polycan (100 and 200 ㎍/㎖) noncytotoxic levels on both myoblast and myotube. Polycan decreased the ROS level overproduced with dexamethasone and improved the depletion of GSH level. Dexamethasone showed a decrease in myotube diameter, which was associated with up-regulation muscle-specific ubiquitin ligases markers, such as atrogin-1, FoxO3, myostatin and muscle RING finger-1 (MuRF1), and down-regulation of myogenin, MEF2, Myogenic regulatory factor 5, 6 and MyoD. The results showed that polycan treatment significantly dose-dependently inhibited it. Furthermore, decreased expressions of PI3K/Akt signal pathway by dexamethasone were reversed by treatment with polycan. Conclusions : Thus, polycan suppresses dexamethasone induced muscle atrophy in C2C12 myotube in vitro model through activation of PI3K/Akt pathway and protective effect of improve skeletal muscle function.

Dynamical Expression of MicroRNA-127-3p in Proliferating and Differentiating C2C12 Cells

  • Li, Jie;Wang, Gaofu;Jiang, Jing;Zhou, Peng;Liu, Liangjia;Zhao, Jinhong;Wang, Lin;Huang, Yongfu;Ma, Youji;Ren, Hangxing
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.12
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    • pp.1790-1795
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    • 2016
  • MicroRNAs (miRNAs) are highly conserved, short non-coding RNAs that regulate gene expression at the posttranscriptional level. Although many miRNAs are identified in muscles and muscle cells, their individual roles are still not fully understood. In the present study, we investigated a muscle highly-expressed miRNA, miR-127-3p, in C2C12 myoblasts and tissues of goats with different muscle phenotypes (Boer vs Wushan black goats). Our results demonstrated that i) miR-127-3p was extensively expressed in tissues of goats; ii) miR-127-3p was higher expressed in muscle, spleen, heart, and skin in the muscular goats (Boer goats) than the control (Wushan black goats). Then we further characterized the dynamical expression of miR-127-3p, MyoD, MyoG, Myf5, Mef2c, and Myosin in the proliferating and differentiating C2C12 myoblasts at day of 0, 1, 3, 5, and 7 in culture mediums. Especially, we found that miR-127-3p was significantly higher expressed in the proliferating than differentiating cells. Our findings suggest that miR-127-3p probably plays roles in the proliferation and differentiation of myoblasts, which further underlies regulation of muscle phenotype in goats.

Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System

  • Li, Yuwen;Piao, Longzhen;Yang, Keum-Jin;Shin, Sang-Hee;Shin, Eul-Soon;Park, Kyung-Ah;Byun, Hee-Sun;Won, Min-Ho;Choi, Byung-Lyul;Lee, Hyun-Ji;Kim, Young-Rae;Hong, Jang-Hee;Hur, Gang-Min;Kim, Jeong-Lan;Cho, Jae-Youl;Seok, Jeong-Ho;Park, Jong-Sun
    • Toxicological Research
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    • v.24 no.3
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    • pp.175-182
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    • 2008
  • DNA-dependent protein kinase(DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be $2^{nd}$ upstream kinase for protein kinase B(PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells(MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK(M059J) and a wild-type of DNA-PK(M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.

The Effect of Miso Facial Acupuncture on Facial Reduction and Improvement of Skin Condition (미소안면침의 얼굴 축소 및 피부상태 개선 효과)

  • Kwon, Gi-Sun;Kim, Jung-Hee;Lee, Kyeong-A;Lee, Soo-Jung;Song, Jeong-Hwa;Song, Choon-Ho;Youn, Hyoun-Min;Jang, Kyung-Jeon;Kim, Cheol-Hong
    • Journal of Acupuncture Research
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    • v.29 no.4
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    • pp.7-18
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    • 2012
  • Objectives : The purpose of this study is to evaluate the effects of Miso facial acupuncture on facial reduction and improvement of skin condition. Methods : From March to May 2012, 20 women in their twenties to forties with no facial diseases were recruited. Miso facial acupuncture was performed on the both side of their face twice a week, total seven times. The 3D face photographs of each participant were checked 5 times ; before treatment, after 1st treatment, 4th treatment, 7th treatment and 10 days from the last treatment using RS-400FL(Morpheus Co. Korea) and REAL FACE. The surface distances of the 4 lines on the face were measured using Renai MEF program. The improvement of skin condition was evaluated by water content, trans epidermal water loss(TEWL), erythema index and melanin index using MPA 5. They were checked 4 times ; before treatment, 4th treatment, 7th treatment and after 10 days from the last treatment. We analyzed data using Paired t-test(p<0.05) and Wilcoxon signed rank test(p<0.05). Results : One case was dropped out due to pain and edema after 4th treatment. The surface distances of the 4 lines on face were significantly reduced and maintained after 10 days from last treatment. Water content was significantly increased and maintained after 10 days from last treatment. TEWL was significantly decreased. Erythema index was significantly decreased from the 3rd evaluations. Melanin index was slight decreased with no significance at the 2nd evaluations. Conclusions : These results show that Miso facial acupuncture can reduce sizes of the face and improve skin condition such as water content, TEWL and erythema index except melanin index.