• 한국영양학회:학술대회논문집
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• 한국영양학회 1995년도 추계학술대회 초록
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• 한국수산과학회지
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• 제52권5호
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• pp.474-481
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• 2019

This study evaluated the chronic effects of $NO_3-N$ on juvenile blackhead seabream Acanthopagrus schlegelii. The experiment used six identically configured recirculating aquaculture systems (435 L), with three tanks (70 L) each. The $NO_3-N$ concentrations studied were 0 (control), 62.5, 125, 250, 500, and 1,000 mg/L $NO_3-N/L$. Thirty juvenile blackhead seabream ($18.8{\pm}2.2g$) were stocked in each tank. Growth and hematological changes were evaluated after 120 days. At the end of the experiment, the growth, survival, and cortisol levels indicated that blackhead seabream were healthy in 500 mg $NO_3-N/L$. However, insulin-like growth factor I (IGF-1) and the IGF-1 receptor were significantly lower at 250, 500, and 1,000 mg $NO_3-N/L$ than in controls (62.5 and 125 mg $NO_3-N/L$). Juveniles were likely affected at a much lower $NO_3-N$ concentration than 250 mg/L $NO_3-N/L$ in terms of IGF-1 and the IGF-1 receptor. Therefore, for the sake of long-term fish welfare, the $NO_3-N$ should be maintained at lower than 250 mg/L for blackhead seabream in recirculating aquaculture systems.

• 한국수정란이식학회지
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• 제11권2호
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• pp.111-124
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• 1996

The present study was carried out to investigate the effects of co-culture cells and growth factors on in vitro culture of Korean native cattle(KNC) embryos fertilized in vitro. Two-eight cell embryos were cultured in vitro using 4 types of co-culture cells and 3 growth factors singly or in combination. The results were as follows, In the co-culture of 2~8 cell embryos with bovine oviductal epithelial cell(BOEC), granulosa cell(BGC), uterine epithelial cell(BUEC) and mouse embryonic fibroblast (MEF) monolayers, the developing rate to blastocysts was significantly(P<0.05) higher with BUEC(32.1%) than with MEF(15.3%), BGC(13.2%) and non co-culture control(11.6%). When the morula co-cultured with BOEC for 5 days following in vitro fertilization were co-cultured with BOEC continuously or with BUEC, respectively, the developing rate to blastocysts was higher with BUEC(73.9%) than with BOEC(56.0%). To examine the effects of growth factors on in vitro development of 2~8 cell embryos, epidermal growth factor(EGF), transforming growth factor-$\beta$l(TGF-$\beta$l) and insulin-like growth factor-1(IGF-1) were added singly or in combination to TCM 199 maturation medium with respective concentration. In a addition of each 10, 30 and SOng /rnl EGF, the developing rate to blastocysts was the highest in lOng /ml EGF(25.3%). In addition of each 1, 2 and Sng /mi TGF-$\beta$1, the developing rate to blastocysts was the highest in lng /ml TGF-$\beta$1(28.8%). In addition of each 50, 100ng/ml JGF-l, the developing rate to blastocysts was higher in 100ng/ml IGF-l(16.5%) than in SOng/mi IGF-1(12.9%). When lOng /ml EGF and lng /ml TGF-$\beta$l was added singly or in combination, the developing rate to blastocysts was similar in groups added singly or in combination with EGF and TGF-$\beta$l (23.l~24.6%), although higher than in control(16.7%). In the co-culture of 2~8 cell embryos Wth BOEC + each 10, 30 and 5Ong /rnl EGF, the developing rate to blastocysts was significantly(p<0.05) higher in BOEC + long /ml EGF(32.3%) than in BOEC + 3Ong /ml EGF(18.9%) and BOEC + song /ml EGF(9.7%). In the co-culture of 2~8 cell embryos with BOEC + each 1, 2, Sng /ml TGF-$\beta$l the developing rate to blastocysts was higher in BOEC + Sng/rnl TGF-$\beta$l(28.2%) than in BOEC + lng /ml TGF-$\beta$l(21.7%) and BOEC + 2ng/ml TGF-$\beta$l(21.4%). In summary, higher developing rate to blastocysts were obtained with co-culture of BUEC for co-culture system, with addition of lOng /ml EGF or lng /ml TGF-$\beta$l for growth factor culture system, and with co-culture of BOEC + lOng /ml EGF or BOEC + Sng /ml TGF-$\beta$l for co-culture + growth factor culture system.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7427-7431
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• 2013

Aims: To examine the pretreatment effects of regular aerobic training on the IGF system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity in rats. Materials and Methods: Forty-eight male rats were divided into groups:(1) control+placebo (2) $control+DOX_{10}mg{\cdot}kg^{-1}$ (3) $control+DOX_{20}mg{\cdot}kg^{-1}$ (4) training+placebo (5) $training+DOX_{10}mg{\cdot}kg^{-1}$ (6) $training+DOX_{20}mg{\cdot}kg^{-1}$. Hepatotoxicity was induced by DOX with dosages of 10 and 20 $mg{\cdot}kg^{-1}$. The rats in groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5 days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, $DOX_{10}mg{\cdot}kg^{-1}$ and $DOX_{20}mg{\cdot}kg^{-1}$, respectively. Results: Administration of $DOX_{20}mg{\cdot}kg^{-1}$ caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the control+placebo group. However, after six weeks of aerobic training and DOX treatment with $10mg{\cdot}kg^{-1}$ and or/ $20mg{\cdot}kg^{-1}$ an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to $C+DOX_{10}$ and $C+DOX_{20}$. Conclusions: Hepatotoxicity of doxorubicin is dose-dependent and pretreatment with regular aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

• Animal Bioscience
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• 제35권7호
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• pp.989-998
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• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

• Asian-Australasian Journal of Animal Sciences
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• 제31권1호
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• Tuberculosis and Respiratory Diseases
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• 제52권4호
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• pp.338-345
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• 2002

연구배경: 본 연구는 진폐증의 폐섬유화에 관여하는 사이토카인 중 PDGF-BB와 IGF-1의 혈청내 농도를 측정 비교함으로서 폐섬유화 관정에서의 역할을 간접적으로 확인하고 진폐증 진단의 생화학적 지표자로서 의미가 있는지 알아보고자, 충주의료원과 연세대학교 원주의과대학 원주기독병원에 내원한 환자를 대상으로 정상대조군과 단순형 석탄광부 진폐증군, 복잡형 석탄광부 진폐증군으로 나누어 혈청내 PDGF-BB와 IGF-1 농도를 측정하여 다음과 같은 결과를 얻었다. 방 법: 직업력과 방사선학적 소견으로 석탄광부 진폐증으로 진단된 환자중 단순형 석탄광부 진폐증 13예와 복잡형 석탄광부 진폐증 17예, 정상 대조군 10명을 대상으로 하였다. Human PDGF-BB immunoassay kit (R&D system, Minneapolis, MN)와 Human IGF-1 immunoassay kit (R&D system, Minneapolis, MN)를 이용하여 각 대상의 혈청내 PDGF-BB와 IGF-1의 농도를 측정하였다. 결 과: 1. 복잡형 석탄광부 진폐증군에서의 혈청 PDGF-BB 농도($10083.76{\pm}5639.07pg/mL$)가 정상 대조군 ($3726.17{\pm}1292.20pg/mL$)이나 단순형 석탄광부 진폐증($8493.88{\pm}5848.51pg/mL$)에 비해 통계학적으로 유의하게 높았다(P<0.05). 2. 정상대조군 ($413.40{\pm}61.94ng/mL$)과 단순형 석탄광부 진폐증($366.77{\pm}183.67ng/mL$), 복잡성 석탄광부 진폐증($403.40{\pm}115.39ng/mL$)의 혈청 IGF-1 농도는 각 군간 통계학적 유의한 차이는 관찰되지 않았다(P>0.05). 3. 작업년수에 따른 혈청 PDGF-BB와 IGF-1의농도는 통계학적으로 유의한 차이가 없었다(P>0.05). 결 론: 이상의 결과를 종합하여 보면 석탄광부 진폐증군에서 혈청내 PDGF-BB 농도의 증가는 폐섬유화 진행을 나타내는 생화학적 지표로서의 의미를 갖는 것으로 생각된다.

• 생명과학회지
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• 제16권7호
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• pp.1133-1140
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• 2006

E. coli HtrA (High temperature requirement protein A)의 human homologue 중 하나인 HtrA1은 IGFBP를 절단하여 IGF의 활동을 조절하는 serine protease으로 알려졌다. HtrA1의 serine protease 활성이 여러 질병의 발병 mechanism과 연관성을 가진 것으로 예상되고 있지만, 이런 상관관계를 밝히기 위해서 기본적으로 필요한 다량의 HtrA1 단백질의 발현 및 정제조건과 HtrA1 serine protease의 최적 활성조건이 확립되어 있지 않은 상황이다. 따라서 본 연구에서는 pGEX 시스템을 이용하여 E. coli에서 mature HtrA1인 ${\Delta}149(WT)$와 catalytic site mutant인 ${\Delta}149(S328A)$를 85%의 순도로 1 liter 배양 시, 정제된 단백질을 각각 $400{\mu}g,\;520{\mu}g$ 얻을 수 있는 발현조건을 정립하였다. 또한 HtrA1 serine protease 활성은 protease의 농도와 substrate와의 반응시간에 dependent하며, substrate와의 반응온도가 $42^{\circ}C$일 때 최적의 serine protease활성을 나타내는 것을 알 수 있었다. 특히 $200{\mu}M$의 HtrA1 serine protease를 $37^{\circ}C$에서 3시간 반응 시켰을 때, substrate로 사용한 ${\beta}-casein$의 약 50%가 절단되는 것을 관찰하였다. 따라서 이 반응조건에 사용한 HtrA1의 양을 1 unit으로 하여 HtrA1의 serine protease활성을 여러 조건에서 비교 분석할 수 있다 본 연구에서 정립한 mature HtrA1을 다량으로 얻을 수 있는 발헌 및 정제조건과 serine protease 최적 활성조건은 HtrA1의 serine protease 활성과 생물학적 기능의 상관관계를 이해하는데 활용될 수 있을 것이다.

• 한국가축번식학회지
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• 제23권2호
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• pp.105-111
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• 1999

본 연구는 한우 난소의 황체세포를 분리ㆍ체외배양하여 progesterone 과 IGF-I 분비기능에 대한 비장세포의 첨가효과를 검토하여 난소기능에 대한 기초정보를 제공하는데 있다. 도축장에서 도축되는 한우 난소로부터 황체를 분리ㆍ효소처리하여 LLC 와 SLC (1$\times$$10^{6}$ cells/$m\ell$)를 회수하였으며 10% FCS와 antibiotic가 첨가된 D-MEM 배양액에 24 시간 체외배양하였다. 비장세포는 성숙한 거세한우의 비장에서 회수하여 5%, 10% 및 20%를 황체세포에 각각 첨가하여 공배양하였다. 황체일령별 조직내 progesterone 농도는 발정주기 중 중기황체 (CL-3)가 유의적으로 높았다. 비장세포를 5%, 10% 및 20%를 각각 황체세포에 첨가하여 배양한 결과, 배양액 중의 progesterone 농도는 대조구에 비해 유의적인 차이가 발견되지 않았으나 LH(100ng/$m\ell$) 첨가구와 비장세포 5%, 10%, 20% 첨가와 함께 LH 를 각각 공배양구에서 대조구(LH＋BP)에 비해 유의적 (p＜0.05)으로 높은 progesterone 분비를 나타내었다. 한편, 황체세포의 체외배양에 있어서 IGF-I은 일정하게 분비하였으나 비장세포와 LH＋비장세포 5%, 10% 및 20%와의 공배양은 대조구에 비해 큰 차이가 없었으나 LH 단독처리구만이 대조구에 비해 유의적으로 (p＜0.05) 높은 수준을 보였다. 이상의 결과로, 비장세포는 황체세포에 작용하여 LH 의 progesterone 분비기능을 촉진시킴으로서 황체세포의 progesterone 분비를 촉진하는 기능이 있으나 IGF-I의 분비기능은 없는 것으로 사료된다.