• BMB Reports
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• v.37 no.2
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• pp.153-158
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• 2004

The acid-labile subunit (ALS) is known to interact with the IGF binding protein (IGFBP) in the presence of insulin-like growth factors (IGFs). Studies, however, indicate that ALS forms a doublet with IGFBP3, independent of IGFs. To characterize the structural domain required for the IGF-free ALS-IGFBP3 interaction, seven recombinant human IGFBP3 mutants were generated: three deletion mutants and four site-specific mutants that had altering N-terminal regions of IGFBP3. ALS and IGFBP3 mRNAs were co-injected into Xenopus oocytes, and their products were cross-linked and immunoprecipitated using antisera against ALS or IGFBP3. Among the deletion mutants, the mutant of D40 (deleted in 11-40th amino acids) exerted no effect in the interaction with ALS, while D60 (${\Delta}11$-60) demonstrated a moderate reduction. D88 (${\Delta}11$-88), however, showed a significant decrease. In the case of site-specific mutants, the mutation that alterated the IGF binding site (codons 56 or 80) exerted a significant reduction in the interaction, whereas codons 72 or 87 showed no significant change in the interaction with ALS. The stability of the ALS-IGFBP3 interaction was analyzed according to a time-dependent mode. Consistent with the binding study, mutants on the IGF binding sites (56 or 80) consistently show a weakness in the ALS-IGFBP3 interaction when compared to the mutants that covered the non-IGF binding sites (72 or 87). This study suggests that the N-terminal of IGFBP3, especially the IGF binding site, plays an important role in interacting with ALS as well as in stabilizing the dual complex, independent of IGFs.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.1
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• pp.3-7
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• 2005

The insulin-like growth factors (IGFs), their receptors, and their binding proteins play key roles in regulating cell proliferation and apoptosis. Insulin-like growth factor binding protein-3 (IGFBP3, OMIM #146732) is one of the proteins that bind to the IGFs. IGFBP3 is a modulator of IGF bioactivity, and direct growth inhibitor in the extravascular tissue compartment. We identified twenty-two novel single nucleotide polymorphisms (SNPs) in IGFBP3 gene in Korean cattle (Hanwoo, Bos taurus coreanae) by direct sequencing of full gene including -1,500 bp promoter region. Among the identified SNPs, five common SNPs were screened in 650 Korean cattle; one SNP in promoter (IGFBP3 G-854C), one in 5'UTR region (IGFBP3 G-100A), two in intron 1 (IGFBP3 G+421T, IGFBP3 T+1636A), and one in intron 2 (IGFBP3 C+3863A). The frequencies of each SNP were 0.357 (IGFBP3 G-854C), 0.472 (IGFBP3 G-100A), 0.418 (IGFBP3 G+421T), 0.363 (IGFBP3 T+1636A) and 0.226 (IGFBP3 C+3863A), respectively. Haplotypes and their frequencies were estimated by EM algorithm. Six haplotypes were constructed with five SNPs and linkage disequilibrium coefficients (|D'|) between SNP pairs were also calculated. The information on SNPs and haplotypes in IGFBP3 gene could be useful for genetic studies of this gene.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.3
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• pp.493-499
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• 2000

골감소증 환자의 혈청중에 존재하는 IGFBP-5의 존재와 변화를 검토한 결과, 골감소즈 환자에서는 정상 대조군에 비해 IGFBP-5가 감소하였는데 이 변화는 IGFBP-5의 분해효소가 작용하기 때문인 것으로 나타났다. IGFBP-5에 작용하는 단백질분해효소 저해제중 metallo계인 EDTA 및 1,10-phenanthroline과 seriner계인 aprotinin, heparin, heparin cofactor 2(HC2), heparine+HC2가 IGFBP-5에 대해 저해효과가 크므로 metalloprotease이면서 serine protease의 성질을 가지는 효소들이 IGFBP-5에 작용하였다. IGF-I과 IGF-II 그리고 insulin은 효소 활성에 아무런 영향이 없었다. IGFBP-5의 zymography에서 정상인과 골감소증 환제어서 180 kDa 크기의 band가 나타났고, gelatin zymography에서 정상 대조군의 경우 66 kDa과 97 kDa 정도의 band가 확인되었고 골감소증 환자의 경우는 69 kDa의 band가 확인되었다.

• BMB Reports
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• v.32 no.3
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• pp.266-272
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• 1999

The insulin-like growth factor (IGF) system consisting of IGF-I, IGF-II, IGF-receptors, and IGF-binding proteins (IGFBP) regulates the proliferation of a variety of cancer cell types. To examine whether a decrease in endogenous IGFBP-3 stimulates proliferation or inhibits differentiation, Caco-2 cells, a human colon adenocarcinoma cell line, were stably transfected with an anti-sense IGFBP-3 expression construct or pcDNA3 vector as control. Accumulation of IGFBP-3 mRNA and secretion of IGFBP-3 into serum-free conditioned medium, 9 days after plating, were significantly lower in Caco-2 cell clones transfected with anti-sense IGFBP-3 cDNA compared to the controls. The anti-sense clones grew at a similar rate to the controls for 8 days after plating, but achieved a higher final density between days 10 and 12. The levels of sucrase-isomaltase mRNA, a marker of enterocyte differentiation of Caco-2 cells, were lower in the anti-sense clones examined on day 9. In conclusion, proliferation of Caco-2 cells can be stimulated by lowering endogenously-produced IGFBP-3.

• Korean Journal of Veterinary Research
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• v.46 no.2
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• pp.97-105
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• 2006

All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). $10^{-7}M$ AtRA activated PKC-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA-induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-${\delta}$ activity.

• Journal of Veterinary Clinics
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• v.20 no.3
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• pp.263-273
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• 2003

This study was carried out to investigate the effects of the Korean Safflower (Carthamus inctorius L) seed powder on serum level of hormones and trabecula area during the recovery from osteoporosis induced ovariectomized rats. Four month-old rats were ovariectomized (OVX), remained untreated for 8 weeks, and were subsequently administered safflower seed (0.03 g/kg) every other day 30 for days. We examined the effects of treated safflower seed every 10 days on ovariectomy-related changes in Insulin-like Growth Factors, Insulin-like Growth Factor binding protein-3 (IGFBP-3), Estrogen, Bone-specific alkaline phosphotase, Calcium, and Phospotase in the serum, and also histomorphology of the proximal fibula metaphysis and femur/body weight rate. Ten and 20 days after safflower seed treatment in OVX rats, serum levels of IGF-I, -II and IGFBP-3 were not different from the Sham and OVX groups. In 30 days, serum levels of IGF-I,-II and IGFBP-3 were higher after safflower seed treatment in OVX rats as compared to the other two groups (p<0.05). Bone alkaline phosphatase levels were increased through safflower seed treatment in OVX rats compared to the other two groups in 30 days. There were no differences between OVX and safflower seed treated OVX rats in serum levels of estrogen and femur/body weight rate, but estrogen levels for the sham group were higher than for the other two groups. The safflower seed is increased to serum levels of IGFs, IGFBP-3 and BALP of osteoporosis induced by ovariectomized rats. Thus, we conclude that the safflower seed is a possible role for improvement of osteoporosis induced-ovariectomized rats.

• Clinical and Experimental Reproductive Medicine
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• v.21 no.3
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• pp.273-279
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• 1994

자궁내막이 생체내 insulin-like growth factor binding protein-1(IGFBP-1)의 혈중치를 유지하는데 얼마나 관여하는지를 평가해 보았다. Immunoreactive IGFBP-1의 혈중치의 측정을 위하여, 월경과다를 주소로 내원한 19명의 환자를 대상으로, gynecologic resectoscopy로 자궁내막 박리를 시행하였다. 자궁내막 박리를 시행한 환자의 혈중 IGFBP-1의 평균치는, 시행전과 비교할 때 감소된 소견을 보였으며, 월경주기와는 상관관계가 없었다. 이러한 소견으로 보아, 자궁내막이 혈중 IGFBP-1의 생성원의 하나로 사료되었다.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.5
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• pp.774-778
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• 1998

The effect of insulin-like growth factor-I (IGF-I) on circulating insulin-like growth factor binding proteins (IGFBPs) in the Korean rockfish, Sebastes schlegeli, was assessed after injected of recombinant human IGF-I (6 $\mu$g/100 g body weight). Growth and metabolic status of each fish were assessed by determing body length and body weight changes, and serum glucose concentration. Serum IGF binding proteins concentrations were assessed by the Western ligand blot procedure using $^{125}I$-labeled human IGF-I tracer. The fish received IGF-I were Heavier than the saline-injected control fish after 2 weeks of treatment. Plasma IGFBP-3 concentration inclosed, but plasma IGFBP-1 and glucose levels decreased significantly after administration. Taken together, the findings of this study suggest that human IGF-I is biologically active in Korean rockfish and may be of significance in metabolic and growth-related processes.

• Journal of the korean academy of Pediatric Dentistry
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• v.50 no.3
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• pp.334-346
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• 2023

The aim of this study was to assess the correlation between serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and hand-wrist radiographs using a skeletal maturity indicator (SMI) and the middle phalanx of the third finger (MP3). Hand-wrist radiographs and blood samples from 205 patients aged 7 - 17 years were retrospectively analyzed by two dentists using the SMI stages, MP3 stages, and serum IGF-1 and IGFBP-3 levels. Serum IGF-1 levels were highest at the SMI 6 - 8 and MP3 - G stage and lowest at the SMI 1 - 3 and MP3 - F stage (p < 0.0001). Serum IGFBP-3 levels were highest at the SMI 9 - 10 and MP3 - I stage and lowest at the SMI 1 - 3 and MP3 - FG stage (p = 0.010, 0.030). As a result of Pearson correlation analysis, a relatively high correlation was found between skeletal maturity using the SMI and MP3 stages and serum IGF-1 levels (r = 0.698, 0.622, p < 0.0001). According to the results of this study, serum IGF-1 levels can be used as an auxiliary measure to evaluate the skeletal maturity of children and adolescents in dentistry. The range from the mean serum IGF-1 level of 472 ㎍/L in SMI 6 stage to the mean IGF-1 level of 510.63 ㎍/L in MP3 G stage could be considered as the peak height velocity in clinical practice.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.109-116
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• 1999

Purpose: Insulin-like growth factor(IGF)-I and -II are peptide growth factor whose activity is modulated by interaction with the family of six IGF-binding proteins(IGFBPs). IGF-I is detected in rat kidney and has metabolic and growth effects. This study was designed to examine temporal expression of IGFBPs in kidney during renal development and postischemic regeneration in rat. Method: The expression of IGFBPs in kidney during renal development from 15th day of gestation to adult life by using Northern blot analysis. We also examined the renal IGF-IGFBP axis in uremic rat by using Northern blot and immunohistochemistry. Results: The mRNA of IGFBP-1 and -3 were not or barely detected in fetal stages. However, the mRNA level of IGFBP-1 and -3 were increased gradually from day 7 after birth to adult. In contrast, the mRNA of IGFBP-2 and -5 were highly expressed in fetal stages and maintained almost same levels until day 7 (IGFBP-2) or day 30 (IGFBP-5) after birth, then their levels decreased markedly. The mRNA of IGFBP-4 were expressed moderately in fetal kidney and increased gradually after birth. Interestingly, the mRNA of IGFBP-1 and-4 were induced up to 3-5 fold during maximum regeneration period and were recovered to normal levels after acute ischemic injury. In contrast, the mRNA level of IGFBP-3 and-IGFBPrP-1 were decreased slightly at 1 day after ischemic injury, then recovered to normal level during maximum regeneration period. Conclusion: There were differential expressions of IGFBPs in kidney that can modulate IGF action on developing, differentiating, maintaining, and regenerating renal structure and function.