• 생명과학회지
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• 제30권7호
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• pp.640-650
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• 2020

간, 췌장 및 지방 조직에서 많은 수준으로 합성되는 섬유 아세포 성장 인자 21(FGF21)은 FGF19과 FGF23와 함께 FGF 패밀리의 비정형 구성원에 속해 있다. FGF21은 발현 조직에 따라 endo/paracrine특징을 보여주며, 포도당 대사 및 에너지 항상성을 포함하는 많은 종류의 대사 경로를 조절하고 있다. 생리학적 조건 하에서 많은 종류의 스트레스가 조직 별 FGF21의 합성을 유도한다고 알려져 있고, 이렇게 증가한 FGF21은 위와 같은 스트레스에 적응하거나 방어하기 위한 세포 내 기전을 활성화 시키게 된다. 이 과정에서 peroxisome proliferator-activated receptor gamma (PPARγ) 및 peroxisome proliferator-activated receptor alpha (PPARα)가 지방 및 간 조직에서 FGF21의 발현을 조절하는 대표적인 전사 조절자로 알려져 있다. 지난 10년간의 연구를 통해 약리학적 FGF21 투여는 체중을 감소시키고 비만 마우스 및 2 형 당뇨병 환자에서 인슐린 감수성 및 지단백질 프로파일을 개선시키는 것으로 보고되었고, 이를 바탕으로 FGF21은 제 2 형 당뇨병, 비만 및 비 알콜 성 지방간 질환(NAFLD)의 치료제로서 큰 주목을 받아 왔다. 그러나 조직 별 상이한 FGF21 발현의 역설적 조건 및 생리 약학적 기능의 차이로 인해 FGF21의 이해는 여전히 부족한 수준에 있다. 따라서 본 총설을 통해 FGF21의 조직 특정 기능 및 해당 동작 메커니즘을 포함한 이전 연구들에서 발생하였던 흥미로운 문제를 논의하고, FGF21 아날로그를 이용한 임상 시험의 현 상황을 요약하고자 한다.

• 생명과학회지
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• 제33권3호
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• pp.287-294
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• 2023

건강한 adipose tissue는 대사 항상성 통해 비만을 막는데 중요하다고 할 수 있다. Adipose tissue는 포도당과 지질 대사를 통해 에너지 균형에 중요한 역할을 한다. 영양분 상태에 따라, adipose tissue는 지질을 저장하여 커지기도 하고, 지질 분해를 통해 에너지를 소비하기도 한다. 게다가, adipose tissue는 호르몬 분비기관으로 작용이 부각되고 있다. 다양한 adipose tissue 호르몬이 존재하며, metabolic signaling을 통해 다른장기와 조직에 영향을 준다. 예를 들면, adipose tissue에서 분비하는 대표적인 펩타이드 호르몬(adipokine)은 섭식조절을 위해 뇌의 중추신경을 자극한다. 또한 adipocytes도 염증성 cytokines을 분비하여 adipose tissue의 immune cells을 표적으로 한다. 당연하게도, adipocytes는 지질에서 만들어지는 호르몬(lipokine)이 분비되어 특정 수용체와 결합하여 paracrine 및 endocrine으로 영향을 준다. 이러한 adipose tissue 호르몬에 의한 장기 조직 간의 상호작용을 이해하기 위해서는, 세부적인 adipocytes 및 다른 표적 세포에서 metabolic sig- naling이 규명되어야 한다. 그러므로, 과체중이나 비만의 건강하지 못한 adipose tissue에서는 metabolic sig- naling의 비정상적인 조절이 일어난다고 할 수 있다. 새로운 adipose metabolic signaling을 표적으로 하는 치료제는 항 비만 약물개발을 이끌어 낼 수 있다. 본 총설논문은 비만과 대사질환 관점에서 adipose tissue 호르몬과 metabolic signaling의 최신 연구결과를 요약 정리한다.

• 한국수정란이식학회지
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• 제29권1호
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• pp.1-5
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• 2014

Recent 2 decades, including in vitro maturation (IVM), assisted reproductive technologies (ARTs) achieved noteworthy development. However the efficiency of ARTs with in vitro matured oocytes is still lower than that with in vivo oocytes. To overcome those limitations, many researchers attempted to adapt co-culture system during IVM and consequently maturation efficiency has been increased. The beneficial effects of applying co-culture system is contemplated base on communication and interaction between various somatic cells and oocytes, achievement of paracrine factors, and spatial effects of extracellular matrix (ECM) from somatic cell surface. The understanding of co-culture system can provide some information to narrow the gap between in vitro and in vivo. Here we will review current studies about issues for understanding cu-culture system with various somatic cells to improve in vitro maturation microenvironment and provide bird view and strategies for further studies.

• BMB Reports
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• 제43권8호
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• pp.513-523
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• 2010

Cytokines that bind to and signal through the gp130 co-receptor subunit include interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from contributing to inflammation, gp130 signalling cytokines also function in the maintenance of bone homeostasis. Expression of each of these cytokines and their ligand-specific receptors is observed in bone and joint cells, and bone-active hormones and inflammatory cytokines regulate their expression. gp130 signalling cytokines have been shown to regulate the differentiation and activity of osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor specific gene-knockout mouse models have identified distinct roles for each of these cytokines in regulating bone resorption, bone formation and bone growth. This review will discuss the current models of paracrine and endocrine actions of gp130-signalling cytokines in bone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis.

• BMB Reports
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• 제50권2호
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• pp.58-59
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• 2017

The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

• 한국발생생물학회지:발생과생식
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• 제24권1호
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• pp.1-17
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• 2020

Phthalates and those metabolites have long history in industry and suspected to have deficient effects in development and reproduction. These are well-known anti-androgenic chemicals and many studies have examined the effects of these compounds on male reproduction as toxins and endocrine disruptors. Uterus is a key organ for proper embryo development, successful reproduction, and health of eutherian mammals including women. To understand the effects of the phthalate, the horizontal approach with a whole group of phthalate is best but the known phthalates are huge and all is not uncovered. Di-(2-ethylhexyl) phthalate (DEHP) is the most common product of plasticizers in polymer products and studied many groups. Although, there is limited studies on the effects of phthalates on the female, a few studies have proved the endocrine disrupting characters of DEHP or phthalate mixture in female. An acute and high dose of DEHP has adverse effects on uterine histological characters. Recently, it has been revealed that a chronical low-dose exposing of DEHP works as endocrine disrupting chemicals (EDC). DEHP can induce various cellular responses including the expression regulation of steroid hormone receptors, transcription factors, and paracrine factors. Interestingly, the response of uterus to DEHP is not monotonous and the exposed female has various phenotypes in fertility. These suggest that the exposing of DEHP may causes of histological modification in uterus and of disease in female such as endometriosis, hyperplasia, and myoma in addition to developmental and reproductive toxicity.

• Preventive Nutrition and Food Science
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• 제22권1호
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• pp.1-8
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• 2017

About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic ${\beta}$- and ${\alpha}$-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the pathobiochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of ${\beta}$-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions.

• Clinical and Experimental Reproductive Medicine
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• 제26권2호
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• pp.157-161
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• 1999

Recent studies clearly demonstrated that the novel expression of LH gene in the rat testis, and suggested the local action of the LH-like molecule. The present study was performed to analyze the expression of LH genes in the rat accessory reproductive organs. Expression of LH subunit genes in the rat uterus and epididymis was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) and specific LH radioimmunoassay (RIA). The $LH_{beta}$ transcripts in these organs contained the published cDNA structure, the pituitary type exons 1-3, which encoded the entire $LH_{beta}$ polypeptide. Presence of the transcripts for the ${\alpha}$-subunit in the rat reproductive tissues were also confirmed by RT-PCR. In the LH RIA, significant levels of LH were detected in crude extracts from the rat ovary, uterus and epididymis. The competition curves with increasing amount of tissue extracts were parallel with those of standard peptide, indicating that the immunoreactive LH-like materials in these tissues are similar to authentic pituitary LH molecule. In rat epididymis, the highest amount of immunoreactive LH was detected in corpus area. Our findings demonstrated that the genes for LH subunits are expressed in the rat accessory reproductive organs, and suggested that these extrapituitary LH may act as a local regulator with auto and/or paracrine manner.

• 한국발생생물학회지:발생과생식
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• 제20권2호
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• pp.127-133
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• 2016

Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. Inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage cause of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence.

• Asian-Australasian Journal of Animal Sciences
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• 제16권3호
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• pp.325-330
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• 2003

There exists considerable evidence that insulin-like growth factor-I (IGF-I) is involved in the regulation of ovulation rate and follicle development. IGF-I is believed to modulate the effects of gonadotropins on follicular growth and cell differentiation via paracrine and autocrine mechanisms. Therefore, this study was performed to relate the expression of IGF-I on ovaries and follicles with egg productivity at 60 wk. The egg productivity of 70 KNOC was recorded from 20 to 60 wk. Blood was taken every 10 wk and ovaries and follicles were taken at 60 wk. Serum IGF-I and IGF-I of ovaries and follicles were measured by radioimmunoassay. Based on egg production levels up to 60 wk and ovarian IGF-I expression at 60 wk, respectively. Chickens were divided into two groups, high and low. Egg production and serum IGF-I in the high IGF-I group were higher than those in the low group. Moreover, the IGF-I expression of follicles in the high ovarian IGF-I expression group was higher than that in the low group. These finding are consistent with the report that IGF-I indirectly regulates ovulation in chickens, suggesting that this regulation may play an important role in improved egg productivity.