• Title/Summary/Keyword: dual background model

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Novel DOX-MTX Nanoparticles Improve Oral SCC Clinical Outcome by Down Regulation of Lymph Dissemination Factor VEGF-C Expression in vivo: Oral and IV Modalities

  • Abbasi, Mehran Mesgari;Monfaredan, Amir;Hamishehkar, Hamed;Seidi, Khaled;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6227-6232
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    • 2014
  • Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. The aim of present study was to evaluate the efficacy of novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in terms of their potential to change the VEGF-C expression profile in a rat OSCC model. Materials and Methods: 120 male rats were divided into 8 groups of 15 animals administrated with 4-nitroquinoline-1-oxide to induce OSCCs. Newly formulated doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) and free doxorubicin were IV and orally administered. Results: Results indicated that both oral and IV forms of DOX-MTX-nanoparticle complexes caused significant decrease in the mRNA level of VEGF-C compared to untreated cancerous rats (p<0.05). Surprisingly, the VEGF-C mRNA was not affected by free DOX in both IV and oral modalities (p>0.05). Furthermore, in DOX-MTX NP treated group, less tumors characterized with advanced stage and VEGF-C mRNA level paralleled with improved clinical outcome (p<0.05). In addition, compared to untreated healthy rats, the VEGF-C expression was not affected in healthy groups that were treated with IV and oral dosages of nanodrug (p>0.05). Conclusions: VEGF-C is one of the main prognosticators for lymph node metastasis in OSCC. Down-regulation of this lymph-angiogenesis promoting factor is a new feature acquired in group treated with dual action DOX-MTX-NPs. Beside the synergic apoptotic properties of concomitant use of DOX and MTX on OSCC, DOX-MTX NPs possessed anti-angiogenesis properties which was related to the improved clinical outcome in treated rats. Taking together, we conclude that our multifunctional doxorubicin-methotrexate complex exerts specific potent apoptotic and anti-angiogenesis properties that could ameliorate the clinical outcome presumably via down-regulating dissemination factor-VEGF-C expression in a rat OSCC model.

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

  • Hou, Qiuke;Huang, Yongquan;Zhang, Changrong;Zhu, Shuilian;Li, Peiwu;Chen, Xinlin;Hou, Zhengkun;Liu, Fengbin
    • Journal of Neurogastroenterology and Motility
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    • v.24 no.4
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    • pp.656-668
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    • 2018
  • Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

Perioperative stress prolong post-surgical pain via miR-339-5p targeting oprm1 in the amygdala

  • Zhu, Yi;Sun, Mei;Liu, Peng;Shao, Weidong;Xiong, Ming;Xu, Bo
    • The Korean Journal of Pain
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    • v.35 no.4
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    • pp.423-432
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    • 2022
  • Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORTTM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.

A Study of School program in the Case of Library and Information Science in Korea (한국문헌정보학의 학부제 도입에 관한 연구)

  • Koo Bon-young
    • Journal of the Korean Society for Library and Information Science
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    • v.30 no.2
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    • pp.3-50
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    • 1996
  • At present, Korean universities and colleges are confronted with a strong challenge, within and without, demanding a drastic change or innovation of university education. Discussion on the propulsion of the School Program is now under way as one of the means to reform the university education With such a background in mind, we have considered what should be the desirable course of Library and Information Science in Korea. We have considered the characteristic features and roles of library and information professionals to cope with the now approaching information society and the changing conditons of educational environment We have collected the pros and cons among professors of tile School Program, and investigated the curricula of the three universities which are at present practicing the School Program. Of the 139 professors to whom we have sent the questionnaries, $92(66\%)$ responded, of which the pros were 42 and the cons were 45. The model plan for the School Program is 'departmental school program' $(44\%)$, which purports to adopt 'departmental school program', with the curricula and material resources being utilized in common, or to adopt joint-appointment system with the common utilization of teaching materials and the introduction of a limited dual major system. The argument against introduction the School Program was that because of the peculiar nature of the discipline itself, Library and Information Science can not be merged with any other discipline.

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The Effect of Family Poverty on the School Adjustment of Multi-cultural Adolescents (다문화 청소년의 학교적응에 가구 빈곤이 미치는 영향)

  • Goo, Ja-Min;Yoon, Hee-Sun;Lee, Sang-Rok
    • The Journal of the Korea Contents Association
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    • v.21 no.5
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    • pp.794-807
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    • 2021
  • The purpose of this study is to examine the effect of family poverty on the school adjustment of multi-cultural adolescents in Korea. For this purpose, the 7th data of Multi-cultural Adolescents Panel Study(MAPS) was used and the OLS multiple regression models ware applied. to the analyses. From the result of the OLS model analyses, we found out that family poverty affect significantly on the school adjustment of multi-cultural adolescents. Especially, family poverty has the significant negative(-) effects on academic achievement and friend relationships. These results of this study show that family poverty is an important factor influencing the school adjustment of multi-cultural adolescents. And they confirm that family poverty during period of the adolescent has an important meaning and influence on the aspect of school adjustment as to the multi-cultural adolescents. Implications of this study may be that policy attentions are necessary to not only multi-cultural characteristics but also family background such as poverty in oder to improve the school adjustment of the multi-cultural adolescents. In addition, results of this study suggest that more special support and interventions are requested to the multi-cultural adolescents from poverty families who are suffering dual difficulties such as multi-cultural problems and poverty problem.

Transcriptome profiling identifies immune response genes against porcine reproductive and respiratory syndrome virus and Haemophilus parasuis co-infection in the lungs of piglets

  • Zhang, Jing;Wang, Jing;Zhang, Xiong;Zhao, Chunping;Zhou, Sixuan;Du, Chunlin;Tan, Ya;Zhang, Yu;Shi, Kaizhi
    • Journal of Veterinary Science
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    • v.23 no.1
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    • pp.2.1-2.18
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    • 2022
  • Background: Co-infections of the porcine reproductive and respiratory syndrome virus (PRRSV) and the Haemophilus parasuis (HPS) are severe in Chinese pigs, but the immune response genes against co-infected with 2 pathogens in the lungs have not been reported. Objectives: To understand the effect of PRRSV and/or HPS infection on the genes expression associated with lung immune function. Methods: The expression of the immune-related genes was analyzed using RNA-sequencing and bioinformatics. Differentially expressed genes (DEGs) were detected and identified by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and western blotting assays. Results: All experimental pigs showed clinical symptoms and lung lesions. RNA-seq analysis showed that 922 DEGs in co-challenged pigs were more than in the HPS group (709 DEGs) and the PRRSV group (676 DEGs). Eleven DEGs validated by qRT-PCR were consistent with the RNA sequencing results. Eleven common Kyoto Encyclopedia of Genes and Genomes pathways related to infection and immune were found in single-infected and co-challenged pigs, including autophagy, cytokine-cytokine receptor interaction, and antigen processing and presentation, involving different DEGs. A model of immune response to infection with PRRSV and HPS was predicted among the DEGs in the co-challenged pigs. Dual oxidase 1 (DUOX1) and interleukin-21 (IL21) were detected by IHC and western blot and showed significant differences between the co-challenged pigs and the controls. Conclusions: These findings elucidated the transcriptome changes in the lungs after PRRSV and/or HPS infections, providing ideas for further study to inhibit ROS production and promote pulmonary fibrosis caused by co-challenging with PRRSV and HPS.

MSCs-Derived miR-150-5p-Expressing Exosomes Promote Skin Wound Healing by Activating PI3K/AKT Pathway through PTEN

  • Cheng Xiu;Huining Zheng;Manfei Jiang;Jiaxu Li;Yanhong Zhou;Lan Mu;Weisong Liu
    • International Journal of Stem Cells
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    • v.15 no.4
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    • pp.359-371
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    • 2022
  • Background and Objectives: The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN. Methods and Results: Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its control lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H2O2 to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H2O2-induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H2O2-induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H2O2-induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H2O2-induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN. Conclusions: MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKT pathway through PTEN.

Airway Inflammation and Responses in the Bronchial Asthma Model in Sprague-Dawley Rats Sensitized by Ovalbumin (백서 기관지 천식 모텔에서 난황에 의한 기도염증과 기도반응)

  • Na, Moon-Jun;Lee, Byoung-Hoon;An, Chang-Hyeok;Kim, Jae-Yeol;Park, In-Won;Choi, Byung-Whui;Hue, Sung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.1
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    • pp.33-44
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    • 2000
  • Background: To evaluate airway responses and inflammation to antigen in Sprague-Dawley rat asthma model, we examined airway responses, serial histologic changes of the lung, and the relationship between airway responses and airway inflammation after antigen airway challenge. Methods: Sprague-Dawley rats were sensitized with subcutaneous injection of 10 ${\mu}g$ ovalbumin(OA). Antigen airway challenges were done 14~16 days after sensitization and the sensitized rats were sacrificed 1h($A_E$), 6~8h($A_L$) and 1day($A_D$) after airway challenge, to examine the histologic changes of the lung. Airway responses were measured by body plethysmograph and recorded by enhanced pause(Penh) as an index of airway obstruction 6~8h after antigen challenges. Nonsensitized controls(10 rats) were also challenged with antigen and sacrificed 1 day later. Histopathologic examination of two trachea, large bronchi, small bronchi, and vessels was performed to evaluate the severity of inflammation and eosinophilic infiltration with H&E stain. Results: In 17 of 20 rats(85%) in both groups, we observed airway responses. Among them, an early response(ER) in 15 rats(75%), an dual response in 5(25%), and an late response(LR) only in 2 rats(10%) displayed. There were no significant differences in the severity of inflammation among the trachea, large bronchi, small bronchi and vessels in all groups after antigen challenge(p>0.05) and between early and late responders. The significant eosinophil infiltration was observed in 5 rats(50%) of AL(p<0.05) compared with in AE and controls. Also, eosinophil infiltration was observed in higher trend in LR(57.1%) compared to ER(40%)(p>0.05). Conclusion: Sprague-Dawley rats sensitized with subcutaneous injection of OA showed a significant airway responses to antigen challenge. But antigen challenges caused a little eosinophil infiltration and no significant airway inflammation. Asthma model of Sprague-Dawley rats could be useful for antigen-induced airway responses, but this model has a limitation for the study of human asthma because of no significant pathologic change.

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Application of the Pulsatile Cardiopulmonary Bypass in Animal Model (이중 박동성 인공심폐기의 동물 실험)

  • Shin, Hwa-Kyun;Won, Yong-Soon;Lee, Jea-Yook;Her, Keun;Yeum, Yook;Kim, Seung-Chul;Min, Byoung-Goo
    • Journal of Chest Surgery
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    • v.37 no.1
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    • pp.1-10
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    • 2004
  • Background: Currently, the cardiopulmonary machine with non-pulsatile pumps, which are low in internal circuit pressure and cause little damage to blood cells, is widely used. However, a great number of experimental studies shows that pulsatile perfusions are more useful than non-pulsatile counterparts in many areas, such as homodynamic, metabolism, organ functions, and micro-circulation. Yet, many concerns relating to pulsatile cardiopulmonary machines, such as high internal circuit pressure and blood cell damage, have long hindered the development of pulsatile cardiopulmonary machines. Against this backdrop, this study focuses on the safety and effectiveness of the pulsatile cardiopulmonary machines developed by a domestic research lab. Material and Method: The dual-pulsatile cardiopulmonary bypass experiment with total extracorporeal circulation was conducted on six calves, Extracorporeal circulation was provided between superior/inferior vena cava and aorta. The membrane oxygenator, which was placed between the left and right pumps, was used for blood oxygenation. Circulation took four hours. Arterial blood gas analysis and blood tests were also conducted. Plasma hemoglobin levels were calculated, while pulse pressure and internal circuit pressure were carefully observed. Measurement was taken five times; once before the operation of the cardiopulmonary bypass, and after its operation it was taken every hour for four hours. Result: Through the arterial blood gas analysis, PCO2 and pH remained within normal levels. PO2 in arterial blood showed enough oxygenation of over 100 mmHg. The level of plasma hemoglobin, which had total cardiopulmonary circulation, steadily increased to 15.87 $\pm$ 5.63 after four hours passed, but remained below 20 mg/㎗. There was no obvious abnormal findings in blood test. Systolic blood pressure which was at 97.5$\pm$5.7 mmHg during the pre-circulation contraction period, was maintained over 100 mmHg as time passed. Moreover, diastolic blood pressure was 72.2 $\pm$ 7.7 mmHg during the expansion period and well kept at the appropriate level with time passing by. Average blood pressure which was 83$\pm$9.2 mmHg before circulation, increased as time passed, while pump flow was maintained over 3.3 L/min. Blood pressure fluctuation during total extracorporeal circulation showed a similar level of arterial blood pressure of pre-circulation heart. Conclusion: In the experiment mentioned above, pulsatile cardiopulmonary machines using the doual-pulsatile structure provided effective pulsatile blood flow with little damage in blood cells, showing excellence in the aspects of hematology and hemodynamic. Therefore, it is expected that the pulsatile cardiopulmonary machine, if it becomes a standard cardiopulmonary machine in all heart operations, will provide stable blood flow to end-organs.

A Study on Medium-Sized Enterprises of Japan (일본의 중견기업에 관한 연구 : 현황과 특징, 정책을 중심으로)

  • Kang, Cheol Gu;Kim, Hyun Sung;Kim, Hyun Chul
    • Korean small business review
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    • v.32 no.2
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    • pp.209-223
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    • 2010
  • Korea's business is composed of a few large-sized enterprises (which can be abbreviated as LSE) and a majority of small-sized enterprises (SSE). Although there has been a growing recognition of the need for the development of medium-sized enterprises (MSE) which can serve as a link between SSE and LSE, as yet there has not yet been a consensus on the definition, characteristics and the function of the MSE in Korea. Nowadays, the world is being globalized, and Japan and China are in competition to ne a great economic power. While East Asia is experiencing rapid changes, promoting MSE which can secure flexibility and efficiency through covering up the limitation of LSE and SSE is needed in order to respond the global market which is being specialized. The features of MSE in Japan can be listed as follows. First, the MSE in Japan is developing the company through getting into niche markets which are hard for major companies to enter rather than developing markets in order to compete against major companies directly. While MSEs are endeavoring to build the business firmly in the domestic market, they can possess special and competitive technical skills through trials and errors; so that they can get a chance develop their business through independent business system rather than putting their effort to compete against major companies. Second, from the MSEs with competitive edge in the market, there are many contributions to the national exportation. Those MSEs produce in domestic and maintain the quality of high price products which need cutting-edge technology, while they relocate the low and middle priced goods to the country where manufacturing costs are low, so that they can maintain the price competitiveness. Third, the industrial structure in Japan is formed from dual structure between major companies and small sized companies. In other words, in Japan's industrial structure which are composed of subcontract structure, this dual structure has taken a major role of small sized companies' growth and manufacturing businesses' international competitive power. Forth, MSE in Japan adopt a strategy of putting their value on qualitative scale growth rather than quantitative scale growth. In this paper, the case of Japanese MSE is analyzed. Along with its long history of Industrialization, Japan has a corporate environment where the SSEs can develop as a MSE and later a LSE through a full-support system. Among its SSEs, there are a number of world class corporations equipped with a large domestic market, win-win cooperation with the LSEs and an independent technology development. It can also be observed that these SSEs develop into MSEs with sustainable growth potentials. This study will focus on the condition under which the MSEs of Japan have been developed, and how they have survived the competition between SSEs and LSEs. Through this study, this paper attempts to offer solutions to Korea's polarization between the SSE and LSE, while providing the basis for SSEs revitalization. In general, if both extremities phenomenon deepen between LSE and SSE, there are possible fears of occurring disutility in national economy by the monopolization of LSE. For that reason, enterprise group, which can make SSE or MSE compete LSE in some area and ease the monopoly and oligopoly problem, is needed. This awareness has been shared for ages long. Nevertheless, there is no legal definition for MSE in Japan, and there is no definition about the enterprise size or unified view of MSE between scholars, but it is defined differently by each of academical person or research institution and study meeting. For that reason, this paper will organize the definition of MSE in Japan, and then will propose the characteristics of the background which has made MSE secure competitiveness and sustainable growth in global market. This study focus on that because through this process, the positive change to the awareness of MSE can be proposed in Korea and to seek the policy direction for building institutional framework which can make SSE become MES. Through this way, the fundamentals for SSE to become MSE can be managed and some appropriate suggestions which will be able to make MSE enter the global market in the future can also be proposed. Due to these facts, this study is very important and well timed task. In a sense of this way, this study will examine the definition and role of MSE in Japan. after this examination, this study will deal with the status, special feature, and promotion policy for MSE. Through this analysis of MSE in Japan, the foundation which be able to set the desirable role model for MSE in Korea can be proposed. Also, the political implication which is needed to push ahead to contribute to creating employment and economic growth through sustainable growth of MSEs in economic system of Korea can be offered through this study. It has been found that Japan's MSE functions as an indispensable link among various industrial structures by holding a significant position in employment rate, production and value added. Although the MSEs took up less than 1% of the entire number of businesses with 2700 manufacturing firms and 7000 non-manufacturing firms, its employment ratios are about 15%, while taking about 25% of the manufacturing industry's exports. In industries such as machinery and electronics which is considered Japan's major industry, the MSEs showed a higher than average ratio of manufacturing exports and employment rate. It can be analyzed that behind Japan's advantageous industries, close and deeply knit MSEs exist. Although there are no clearly stated policies geared towards the MSEs by the Japanese government, various political measures exist such as the R&D Project and the inducement of cooperation between enterprises which gives room for MSEs to participate in the SSE policies. In relation to these findings, the following practical measures can be considered in order to revitalize Korea's MSEs: First, there is a need for a legal definition of MSE and the incentives to provide legal support for its growth. Second, if a law to support the MSEs is established, it could provide a powerful inducement for the SSE to grow as a MSE, rather than stay as a SSE. Third, there is a need for a strategy of MSEs to establish a stable base in the domestic market and then advance to the global market with the accumulated trial and error and competitiveness. Fourth, the SSE themselves need the spirit of entrepreneurship in order to make the leap to a MSE. Because if nothing is to be changed about the system on the firms that grew, and the parts of the past custom was left to be managed alone, confusion and absence of management can take place. No matter how much tax favors the government will give and no matter how much incentive there could be through the policies, there are limits for industries to higher the ability to propagate. And because of that it is a period where industries need their own innovative skills to reform their firms.