• Reproductive and Developmental Biology
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• 제38권1호
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• pp.21-34
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• 2014

The majority of early embryonic mortality in pregnancy occurs during the peri-implantation stage, suggesting that this period is important for conceptus viability and the establishment of pregnancy. Successful establishment of pregnancy in all mammalian species depends on the orchestrated molecular events that transpire at the conceptus-uterine interface during the peri-implantation period. This maternal-conceptus interaction is especially crucial in pigs because in them non-invasive epitheliochorial placentation occurs, in which the pre-implantation phase is prolonged. During the pre-implantation period, conceptus survival and the establishment of pregnancy are known to depend on the developing conceptus receiving an adequate supply of histotroph, which contains a wide range of nutrients and growth factors. Evidence links growth factors including epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), vascular endothelial growth factor (VEGF), and colony-stimulating factor 2 (CSF2) to embryogenesis or implantation in various mammalian species; however, in the case of pig, little is known about such functions of these growth factors, especially their regulatory mechanisms at the maternal-conceptus interface. Our research group has presented evidence for promising growth factors affecting cellular activities of primary porcine trophectoderm (pTr) cells, and we have identified potential intracellular signaling pathways responsible for the activities induced by these factors. Therefore, this review focuses on promising growth factors at the maternal-conceptus interface regulating the development of the porcine conceptus and playing pivotal roles in implantation events during early pregnancy in pigs.

• 생명과학회지
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• 제21권2호
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• pp.242-250
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• 2011

본 연구에서는 C2C12 근육 세포에서 IGF-I이 리간드 비의존적으로 엔드로젠 수용체 coactivator 유전자 발현에 미치는 영향에 대해 알아보았다. 그 결과 IGF-I 이 리간드 비의존적으로 엔드로젠 수용체의 coactivator인 GRIP-1, SRC-1, ARA70 유전자들의 단백질과 mRNA 발현을 증가시켰으며, p38 MAPK와 ERK1/2 신호전달 경로 억제제인 SB203580과 PD98059를 IGF-I과 함께 처리한 결과 IGF-I에 의한 엔드로젠 수용체 coactivator 유전자 발현의 증가를 감소시켰음을 알 수 있었다. 엔드로젠 수용체 coactivator가 엔드로젠 물질이 없이도 IGF-I에 의해 발현이 증가하였다는 사실은 운동에 의해 근육에서 분비가 증가하는 IGF-I이 리간드 비의존적으로 근육 세포에서 엔드로젠 수용체 활성화 안정에 기여하는 엔드로젠 수용체 coactivator를 활성화 시킬 수 있다는 사실을 증명 하였다는데 의의가 있다고 사료된다. 또한, IGF-I의 하부신호전달 경로로 잘 알려진 p38 MAPK와 ERK1/2 신호전달 경로를 차단하였을 때는 발현이 억제되었는데 이를 통해 IGF-I이 근육세포 내에서 p38 MAPK, ERK1/2 경로를 통해 엔드로젠 수용체 coactivator 발현에 중요한 역할을 한다는 사실을 확인할 수 있었다. 이러한 결과는 근육에서 중요한 기능을 담당하는 IGF-I이 엔드로젠 수용체 coactivator 유전자 발현을 조절하는 기능이 있으며 이러한 IGF-I에 의한 리간드 비의존적인 엔드로젠 수용체 coactivator 유전자 발현 조절에 있어 p38 MAPK와 ERK1/2는 필수적인 신호전달 경로임을 확인하였다는 데서 그 의의가 있다고 할 수 있겠다. 향후 다양한 성장인자들에 의한 coactivator 발현에 관한 연구를 비롯하여, corepressor의 발현 억제 기능 및 신호전달 경로에 관한 연구가 추가적으로 이루어져야 할 것이다.

• BMB Reports
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• 제50권4호
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• pp.160-161
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• 2017

Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remains largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activity of NMD decreases during aging, raising the possibility that RNA quality declines in old animals. We then show that key components of NMD complex are required for prolonged lifespan in C. elegans. In addition, animals with reduced insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS), a representative longevity model, display increased NMD activity. Thus, up-regulation of NMD appears to play crucial roles in longevity conferred by reduced IIS via enhancing mRNA quality control. As both IIS and NMD pathways are evolutionarily conserved, mammals including humans may be equipped with similar RNA quality control systems to achieve longevity.

• Fisheries and Aquatic Sciences
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• 제18권4호
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• pp.417-420
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• 2015

We investigated the relationship between viability and IGF-1 receptor (IGF-1R) activity in D-shaped and umbo larvae of the surf clam Spisula sachalinensis after treatment with vitrification solution (VS) or freezing. In a toxicity assay, VS1, containing 5 M dimethyl sulfoxide (DMSO), was very harmful to D-shaped and umbo larvae. However, VS2, containing 5 M ethylene glycol (EG), was not harmful to either larval stage. Although VS2 had a promising toxicity test outcome, none of the larvae survived vitrification. After immersion into VSs and freezing, IGF-1R ${\beta}$-subunits were detected in all larvae; however, tyrosine phosphorylation of intracellular ${\beta}$-subunits was detected only in the control and live groups. These results suggest that activation of IGF-1R may influence surf clam larvae viability.

• Food Science and Biotechnology
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• 제16권6호
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• pp.1046-1050
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• 2007

To investigate the growth promoting effects of an herbal medicine formulation (HM-10), Sprague Dawley (SD) male rats (3 weeks old) were divided into 3 groups (8 rats/group). The control group was given a daily oral administration of saline, and the treatment groups, HM-1 and HM-2, were given daily administrations of HM-10 (500 and 1,000 mg/kg BW, respectively). The cumulative tibial bone growth of the HM-1 and HM-2 groups (22.5 and 20.8 mm, respectively), and their cumulative femur bone growth (19.4 and 18.2 mm, respectively), were significantly different compared to the control group (7.5 mm of tibial growth and 7.7 mm of femur growth) (p<0.05). Lastly, the growth hormone levels of the HM-1 and HM-2 groups (1.70 and 1.79 ng/mL, respectively), as well as their insulin like growth factor 1 (IGF-1) levels (165.1 and 171.7 ng/mL, respectively) showed significant differences compared to the control (0.93 ng/mL of growth hormone and 125.6 ng/mL of IGF-1) (p<0.05).

• 대한본초학회지
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• 제24권1호
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• pp.121-131
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• 2009

Objectives：This study was designed to investigate the effects of herbal composition and fermented Cervi Pantotrichum Cornu on the growth of longitudinal bone in the adolescent male rats. Methods： Longitudinal bone growth was measured by fluorescence microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate and the induction of local insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were measured. Results： The herbal composition treatment enhanced longitudinal bone growth and total heght of growth plate and promoted the induction of local IGF-1 and BMP-2 of growth plate. Conclusions： This study showed that the herbal composition have the effect of bone growth in adolescent rats and might be used for the growth delayed adolescent and inherent growth failure patient.

• Journal of Animal Science and Technology
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• 제45권1호
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• pp.33-40
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• 2003

본 연구는 혈장의 insulin-like growth factor (IGF)-I과 IGF-II 농도와 산자수 및 비유성적과의 관계를 구명하고자 착수되었다. 분만주가 비슷한 미경산 및 경산 임신돈 중에서 선발한 총 60두의 순종 Landrace와 Yorkshire 공시돈을 저산자수 (low; <${\mu}$­0.5 SD)와 고산자수 (high; >${\mu}$ + 0.5 SD)-lines로 구분하여 2 (품종) ${\times}$ 2 (line) 요인분석 실험설계 하에 본 실험을 진행하였다. 공시돈은 분만시 모돈당 포유자돈수를 9두로 고정시키고, 3주령 이유시 비유량의 척도로서 총 이유자돈 체중을 측정하였다. 혈액 시료는 임신 90일과 분만 후 15일에 경정맥으로부터 채취하였다. 본 실험기간 중 산자수 및 본 실험기간까지의 평균 산자수는 high-line이 low-line보다 각각 3.7두와 2.4두 많았고 (P< 0.01), 두 품종간 산자수 차이는 없었다. 임신 90일 혈장의 IGF-II 농도는 low-line보다 high-line에서 높았다. 산자수는 임신 90일 IGF-I 농도와 Landrace에서는 부의 상관관계를 나타냈고 (r=－0.46; P<0.05), Yorkshire에서는 부의 상관관계 경향을 나타내어 (r=－0.31; P=0.09) 전체 공시돈에서는 이들 두 변수간 유의적인 부의 상관관계를 보였다 (r=－0.35; P< 0.01). 이유시 모돈당 총 이유자돈 체중은 두 품종간 혹은 두 lines간 차이가 없었다. 이유자돈 체중과 IGF 농도와의 관계는 품종 ${\times}$ 생리적인 생태 조합들간 일정한 경향을 나타내지 않았다. 이상의 결과는 임신 90일 IGF 농도가 임박한 분만시 산자수의 지표가 될 수 있는 가능성을 시사한다.

• 대한본초학회지
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• 제29권5호
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• pp.31-38
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• 2014

Objectives : Egg yolk is composed of various important chemical substances for human health. A calcium shortage causes the growth retardation on the body growth. In this study, we examined the therapeutic effects of calcium, vitamin D and egg yolk peptide (EYP) treatment on the retardation of the longitudinal bone growth induced by low-calcium diet in adolescent rats. Methods : Low calcium diets were administrated for 15 days. During the last five days, calcium and/or vitamin D and/or EYP were administrated. The body weights, longitudinal bone growth rates, the heights of growth plates, and bone morphogenetic protein (BMP)-2 and insulin-like growth factor (IGF)-1 expressions were measured using histochemical analysis. Results : Low calcium diets caused the significant reduction in body weight gains and the longitudinal bone growth. The heights of growth plates and the expressions of BMP-2 and IGF-1 showed the impairment of body growth as well. Calcium and/or vitamin D administration could not significantly increase the longitudinal bone growth. However, calcium, vitamin D, and EYP administration significantly increased the bone growth, the growth plate height, and BMP-2 and IGF-1 expressions. Conclusions : These results suggest that EYP enhances the longitudinal bone growth in the calcium and/or vitamin D deficiency and it could be a promising agent for the treatment of children suffering from malnutrition.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.297-304
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• 2016

Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.

• Reproductive and Developmental Biology
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• 제30권2호
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• pp.93-97
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• 2006

To study the signaling effect of insulin-like growth factor-I(IGF-1), transgenic mice containing IGF-1 Receptor (IGF-1R) cDNA fused to metallothionein promoter were produced by DNA microinjection into the pronucleus of mouse zygote. Three founders were produced with transgenic mice containing IGF-1R gene. Transgenic mice lines contained approximately $4{\sim}20$ copies of transgenes per cell and transmission of this gene into the progeny with Mendelian manner were determined. The founder mice were mated with normal mice to produce $F_1$ mice and then $F_2$ mice. Transmission rates of IGF-1R transgene in the progeny mice were $25{\sim}60%$ in $F_1$ generation and $40{\sim}50%$ in $F_2$ generation. The mRNA expression of IGF-1R transgene in liver was analyzed using RT-PCR for IGF-1R gene in liver. When body weights of transgenic pups were measured during 4, 10 and 14 weeks after birth, IGF-1R transgenic mice grew faster than non transgenic littermates. This study indicated that growth regulation by IGF-1 signaling through IGF-1R can be elucidated using IGF-1R transgenic mice.