• Title/Summary/Keyword: Pathways

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Association of β-Catenin with Fat Accumulation in 3T3-L1 Adipocytes and Human Population (β-catenin 유전자의 3T3-L1 지방세포 및 인체에서의 지방축적 연관성 연구)

  • Bae, Sung-Min;Lee, Hae-Yong;Chae, Soo-Ahn;Oh, Dong-Jin;Park, Suk-Won;Yoon, Yoo-Sik
    • Journal of Life Science
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    • v.21 no.9
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    • pp.1301-1309
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    • 2011
  • The major function of adipocytes is to store fat in the form of triglycerides. One of the signaling pathways known to affect adipogenesis, i.e. fat formation, is the WNT/${\beta}$-catenin pathway which inhibits the expression and activity of key regulators of adipogenesis. The purpose of this research is to find genes among the WNT/${\beta}$-catenin pathway which regulate adipogenesis by using small interfering (si) RNA and to find the association of single nucleotide polymorphisms (SNPs) of the gene with serum triglyceride levels in the human population. To elucidate the effects of ${\beta}$-catenin siRNA on adipogenesis key factors, PPAR${\gamma}$ and C/EBP${\alpha}$, we performed real-time PCR and western blotting experiments for the analyses of mRNA and protein levels. It was found that the siRNA-mediated knockdown of ${\beta}$-catenin upregulates adipogenesis key factors. However, upstream regulators of the WNT/${\beta}$-catenin pathway, such as DVL2 and LRP6, had no significant effects compared to ${\beta}$-catenin. These results indicate that ${\beta}$-catenin is a candidate gene for human fat accumulation. In general, serum triglyceride level is a good indicator of fat accumulation in humans. According to statistical analyses of the association between serum triglyceride level and SNPs of ${\beta}$-catenin, -10,288 C>T SNP (rs7630377) in the promoter region was significantly associated with serum triglyceride levels (p<0.05) in 290 Korean subjects. On the other hand, serum cholesterol levels were not significantly associated with SNPs of the ${\beta}$-catenin gene. The results of this study showed that ${\beta}$-catenin is associated with fat accumulation both in vitro and in the human population.

Vibrio Vulnificus Induces the Inflammation of Mouse Ileal Epithelium: Involvement of Protein Kinase C and Nuclear Factor-Kappa B (회장 상피세포에서 비브리오균(Vibrio vulnificus)의 염증 유도 기작 연구: protein kinase C와 nuclear factor kappa-B의 관련성)

  • Han, Gi Yeon;Jung, Young Hyun;Jang, Kyung Ku;Choi, Sang Ho;Lee, Sei-Jung
    • Journal of Life Science
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    • v.24 no.6
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    • pp.664-670
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    • 2014
  • In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.

Anti-inflammatory Activities of an Ethanol Extract of Sargassum macrocarpum in Lipopolysaccharide (LPS)-stimulated RAW 264.7 Macrophages (Lipopolysaccaride로 유도된 Raw 264.7 세포에서 큰열매모자반 에탄올 추출물의 항염증 활성)

  • Cheon, Ji Min;Kim, Hyang Suk;Choi, Eun Ok;Kwon, Da Hye;Choi, Yung Hyun;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1437-1444
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    • 2017
  • Sargassum macrocarpum is a widely distributed marine brown algae found in the North Pacific. The objective of this study was to evaluate the anti-inflammatory activity of an ethanol extract of S. macrocarpum (EESM). First, we investigated the anti-inflammatory activities of EESM in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. EESM treatment suppressed nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production and inhibited the expressions of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, the expression of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-1 beta ($IL-1{\beta}$), was decreased in a dose dependent manner. Investigation of the signaling pathways of nuclear factor kappa B ($NF-{\kappa}B$), phosphoinositide-3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) revealed suppression of $NF-{\kappa}B$ translocation from the cytosol to nucleus by EESM treatment. The phosphorylation of the Akt and ERK proteins was also inhibited by EESM treatment. EESM treatment also stimulated the expression of the heme oxygenase-1 (HO-1) enzyme and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2). These results suggest that EESM has anti-inflammatory activity and could have potential uses in the field of nutraceuticals.

The Immunohistochemical Expression of Nuclear Retinoid Receptor and CREB in Gastric Adenocarcinoma (위선암종에서 핵의 Retinoic Acid Receptor (RAR) 및 cAMP Response Element Binding Protein (CREB)의 면역조직화학적 발현양상)

  • Han, Ho-Sun;Kim, Yong-Seok;Park, Joong-Min;Choi, Yoo-Shin;Cha, Seong-Jae;Kim, Mi-Kyung;Chi, Kyung-Choun
    • Journal of Gastric Cancer
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    • v.8 no.4
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    • pp.182-188
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    • 2008
  • Purpose: Transcriptional factors of CREB (cAMP response element binding protein) are involved in regulating the gene expression in response to a variety of signaling pathways. The proteins produced by the CREB genes play key roles in many physiological processes, including memory and long-term potentiation. The retinoic acid receptor (RAR) axis mediates epithelial cell differentiation and proliferation in many tissues. This study examined the expressions of RAR and CREB and their relationship with the clinicopathologic factors and their significance. Materials and Methods: The levels of the RAR and CREB expressions were measured in 150 gastric adenocarcinomas by performing immunohistochemical staining. Results: 1. An RAR protein expression was found in 63.3% of the adenocarcinomas (95/150) and a CREB expression was found in 60.7% (91/150) of the adenocarcinomas. 2. An RAR protein expression was found in 72.2% (78/108) of the intestinal type adenocarcinomas and in 40.5% (17/42) of the diffuse type adenocarcinomas (P<0.05). Based on the depth of invasion, an RAR protein expression was found in 58.3% (14/24) of the T1 adenocarcinomas, in 61.9% (13/21) of the T2 adenocarcinomas, in 63.5% (61/96) of the T3 adenocarcinomas, in 77.8% (7/9) of the T4 adenocarcinomas and in 74.7% (62/83) of the adenocarcinomas with lymph node metastasis and in 49.2% (33/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 3. A CREB expression was found in 69.4% (75/108) of the intestinal type and in 38.1% (16/42) of the diffuse type (P>0.05). Based on the depth of invasion, a CREB expression was found in 50% (12/24) of the T1 adenocarcinomas, in 52.4% (11/21) of the T2 adenocarcinomas, in 64.6% (62/96) of the T3 adenocarcinomas, in 66.6% (6/9) of the T4 adenocarcinomas, in 71.1% (59/83) of the adenocarcinomas with lymph node metastasis and in 47.8% (32/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 4. The RAR protein and CREB expressions coincided in 71.4% of the gastric adenocarcinomas and a significant correlation between them was found (P<0.05). Conclusion: We found a significant relationship between the expression of RAR and CREB and the histology and lymph node metastasis of gastric cancer. Further studies are needed to confirm their biologic meaning in gastric carcinogenesis.

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Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells (산화적 스트레스에 대한 여주 (Momordica charantia) 추출물의 항산화 효과 및 세포사멸 억제 기전을 통한 신경세포보호효과)

  • Kim, Kkot Byeol;Lee, Seonah;Heo, Jae Hyeok;Kim, Jung hee
    • Journal of Nutrition and Health
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    • v.50 no.5
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    • pp.415-425
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    • 2017
  • Purpose: Many studies have suggested that neuronal cells protect against oxidative stress-induced apoptotic cell death by polyphenolic compounds. We investigated the neuroprotective effects and the mechanism of action of Momordica charantia ethanol extract (MCE) against $H_2O_2-induced$ cell death of human neuroblastoma SK-N-MC cells. Methods: The antioxidant activity of MCE was measured by the quantity of total phenolic acid compounds (TPC), quantity of total flavonoid compounds (TFC), and 2,2-Diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging activity. Cytotoxicity and cell viability were determined by CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Antioxidant enzyme (SOD-1,2 and GPx-1) expression was determined by real-time PCR. Mitogen-activated protein kinases (MAPK) pathway and apoptosis signal expression was measured by Western blotting. Results: The TPC and TFC quantities of MCE were 28.51 mg gallic acid equivalents/extract g and 3.95 mg catechin equivalents/extract g, respectively. The $IC_{50}$ value for DPPH radical scavenging activity was $506.95{\mu}g/ml$ for MCE. Pre-treatment with MCE showed protective effects against $H_2O_2-induced$ cell death and inhibited ROS generation by oxidative stress. SOD-1,2 and GPx-1 mRNA expression was recovered by pre-treatment with MCE compared with the presence of $H_2O_2$. Pre-treatment with MCE inhibited phosphorylation of p38 and the JNK pathway and down-regulated cleaved caspase-3 and cleaved PARP by $H_2O_2$. Conclusion: The neuroprotective effects of MCE in terms of recovery of antioxidant enzyme gene expression, down-regulation of MAPK pathways, and inhibition apoptosis is associated with reduced oxidative stress in SK-N-MC cells.

Projection of Potential Cultivation Region of Satsuma Mandarin and 'Shiranuhi' Mandarin Hybrid Based on RCP 8.5 Emission Scenario (RCP 8.5 기후변화시나리오에 근거한 온주밀감과 '부지화'의 잠재적 재배지 변화 예측)

  • Moon, Young-Eel;Kang, Seok-Beom;Lee, Hyejin;Choi, Young-Hun;Son, In-Chang;Lee, Dong-Hoon;Kim, Sung-Ki;An, Moon-Il
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.19 no.4
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    • pp.215-222
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    • 2017
  • The potential change of the cultivation area of main citrus cultivars, satsuma mandarin (Citrus unshiu Marc.) and 'Shiranuhi' mandarin hybrid [(Citrus unshiu ${\times}$ C. sinensis) ${\times}$ C. reticulata] were determined with base year (1981 to 2010) to 2090. The meteorological data provided by the Korea Meteorological Administration (KMA), and the digital agricultural climate map of 30m-solution based on the Representative Concentration Pathways (RCP) 8.5 was used for projection of potential cultivation area. As a result, the potential suitable region of satsuma mandarin included almost Jeju region during base year. At the 2030s, the potential suitable region of satsuma mandarin increased and the cultivable region also increased focused on the coast region of Jeonnam province. From the 2060s, the suitable area spread out to mountain area of Jeju, Jeonnam, Gyeongnam, and the coast region of Kangwon, and the cultivable region expanded to the area of Gyeongbuk, Chungnam, and Jeonbuk. In the case of 'Shiranuhi' mandarin hybrid, the suitable region included only the partial coast area of Jeju, and cultivable area covered Jeju region and the partial southern coast of Jeonnam during the standard period. At the 2030s, the suitable region of 'Shiranuhi' included the current cultivation area of satsuma mandarin, and the cultivable region moved to northward by the partial southern coast region. At the 2090s, the slightly increased suitable region covered all Jeju regions, Jeonnam, Gyeongnam, and the coast area of Kangwon, and the cultivable region proceeded northward focusing on the coastline. In conclusion, the prediction of the potential land for citrus cultivation based on the RCP 8.5 showed that the suitable region of satsuma mandarin decreased, whereas that of cultivation of 'Shiranuhi' increased. Moreover, it was forecasted that citrus cultivation area would extend to Kangwon region at the end of the $21^{st}$ century.

An Economic Analysis of the Migration Decision: The Case of Korea (우리나라 인구이동결정에 관한 경제적 분석)

  • Lee, Seon
    • Korea journal of population studies
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    • v.10 no.1
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    • pp.70-86
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    • 1987
  • Going beyond the previous formulations of development theories, the present paper explores the effects other than political economy on quality of life in a rapidly developing country. The major analysis takes up the historical trend and nature of the developmental transformation that is partially a consequences of state structures and partially autonomous form it in South Korea. Also, it diagnoses developmental pathways for the future track by constructing a baseline model for state transition on the basis of power game between the state and civil society in the country. The results of the historical analysis show that civil society has been transformed in the course of confrontations and interactions between the state and nationalist social movement. The distinction between developmental(or bureaucratic authoritarian) and democratic state is presented to show that these are two qualitatively different aspects of state of state power, requiring separate analytical treatment. Furthermore, the state-centric approach which emphasizes the active role of the state at the sacrifice of societal fabric-constraining social conditions for quality of life - appears to be modified. On the contrary, the impact of civil society is transmitted both directly and indirectly via labor and ecological movement for quality of life, which is critical to the formation of the welfare state in the country. The prospect for sustainable development in Korea lies in providng and expanding quality of life in terms of the financial feasibility of the state through the public-private cooperation, and abstaining from drastic and radical commitment to welfare services as is the case with the European declines in welfare state, Further studies are needed to examine the interrelationships in different historical and cultural settings of developing counties to estimate a theory of quality of life and social justice.

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Development of Natural Antioxidants and Whitening Agents for Cosmeceuticals

  • Kim, Jong-Pyung
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.79-92
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    • 2007
  • Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

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An Analysis of Epidemiological Investigation Reports Regarding to Pathogenic E. coli Outbreaks in Korea from 2009 to 2010 (최근 2년간(2009-2010) 우리나라 병원성 대장균 식중독 역학조사 보고서 분석)

  • Lee, Jong-Kyung;Park, In-Hee;Yoon, Kisun;Kim, Hyun Jung;Cho, Joon-Il;Lee, Soon-Ho;Hwang, In-Gyun
    • Journal of Food Hygiene and Safety
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    • v.27 no.4
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    • pp.366-374
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    • 2012
  • Recently pathogenic E. coli is one of the main foodborne pathogens resulting in many patients in Korea. To understand the characteristics of pathogenic E. coli outbreaks in Korea, the epidemiological investigation reports of pathogenic E. coli outbreak in 2009 (41 reports) and in 2010 (27 reports) were collected in the web site of the Korea Centers for Disease Control and Prevention, reviewed and analysed in this study. The main places of the pathogenic E. coli outbreaks were food catering service area (64.8%) and restaurants (25.0%). The main type of the pathogens were EPEC (44.7%) and ETEC (34.2%). EAEC and EHEC was responsible for 10.5 and 9.2%, respectively. Eight of 68 outbreak cases were caused by more than 2 types of pathogenic E. coli which implicates the complicated contamination pathways of pathogenic E. coli. The incidence rate of pathogenic E. coli was $33.6{\pm}30.5%$ and the main symptoms were diarrhea, stomach ache, nausea, vomiting, and fever etc. The two identified food sources were identified as frozen hamburger pattie and squid-vegetable mixture. To improve the food source identification by epidemiological investigation, food poisoning notification to the agency should not be delayed, whole food items attributed the outbreak should be collected and detection method of the various pathogenic E. coli in food has to be improved. In conclusion, the characteristics between the EHEC outbreaks in the western countries and the EPEC or ETEC outbreaks in Korea needs to be distinguished to prepare food safety management plan. In addition, the development of the trace back system to find the contamination pathway with the improved detection method in food and systemic and cooperative support by the related agencies are necessary.

The Past and Future of Public Engagement with Science and Technology (참여적 과학기술 거버넌스의 전개와 전망)

  • Kim, Hyomin;Cho, Seung Hee;Song, Sungsoo
    • Journal of Science and Technology Studies
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    • v.16 no.2
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    • pp.99-147
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    • 2016
  • This paper critically reviews the previous discussion over public engagement with science and technology by Science and Technology Studies literatures with a focus on justification and acceptance. Recent studies pointed out that the "participatory turn" after the late 1990s was followed by confusion and disagreement over the meaning and agency of public engagement. Their discussion over the reproduction of the ever-present boundary between science and society along with so-called late modernity and post-normal science and sometimes through the very processes of public engagement draws fresh attention to the old problem: how can lay participation in decision-making be justified, even if we agree that privileging the position of experts in governance of science and technology is no longer justified? So far STS have focused on two conditions for participatory turn-1) uncertainties inherent in experts' ways of knowing and 2) practicability of lay knowledge. This paper first explicated why such discussion has not been logically sufficient nor successful in promoting a wide and well-thought-out acceptance of public engagement. Then the paper made a preliminary attempt to explain what new types of expertise can support the construction and sustainment of participatory governance in science and technology by focusing on one case of lay participation. The particular case discussed by the paper revolves around the actions of a civil organization and an activist who led legal and regulatory changes in wind power development in Jeju Special Self-governing Province. The paper analyzed the types of expertise constructed to be effective and legitimate during the constitution of participatory energy governance and the local society's support for it. The arguments of this paper can be summarized as follows. First, an appropriate basis of the normative claim that science and technology governance should make participatory turn cannot be drawn from the essential characteristics of lay publics-as little as of experts. Second, the type of 'expertise' which can justify participatory governance can only be constructed a posteriori as a result of the practices to re-construct the boundaries between factual statements and value judgment. Third, an intermediary expertise, which this paper defines as a type of expertise in forming human-nonhuman associations and their new pathways for circulations, made significant contribution in laying out the legal and regulatory foundation for revenue sharing in Jeju wind power development. Fourth, experts' conventional ways of knowing need to be supplemented, not supplanted, by lay expertise. Ultimately, the paper calls for the necessity to extend STS discussion over governance toward following the actors. What needs more thorough analysis is such actors' narratives and practices to re-construct the boundaries between the past and present, facts and values, science and society. STS needs a renewed focus on the actual sites of conflicts and decision-making in discussing participatory governance.