• Title/Summary/Keyword: IGF binding protein 3 (IGFBP3)

Search Result 73, Processing Time 0.021 seconds

Regulation of adductor muscle growth by the IGF-1/AKT pathway in the triploid Pacific oyster, Crassostrea gigas

  • Kim, Eun-Young;Choi, Youn Hee
    • Fisheries and Aquatic Sciences
    • /
    • v.22 no.9
    • /
    • pp.19.1-19.10
    • /
    • 2019
  • We investigated the insulin-like growth factor 1 (IGF-1)/AKT signaling pathway involved in muscle formation, growth, and movement in the adductor muscle of triploid Pacific oyster, Crassostrea gigas. Large and small triploid oysters (LTs and STs) cultured under identical conditions were screened, and the signaling pathways of individuals with superior growth were compared and analyzed. mRNA and protein expression levels of actin, troponin, tropomyosin, and myosin, proteins important in muscle formation, were higher in LTs compared with STs. Expression levels of IGF-1, IGF binding protein (IGFBP), and IGFBP complex acid-labile subunit were also higher in LTs compared with STs. Phosphorylation of the IGF receptor as well as that of AKT was high in LTs. In addition, the expression of phosphomammalian target of rapamycin and phospho-glycogen synthase kinase $3{\beta}$ was increased and the expression of Forkhead box O3 was decreased in LTs. Therefore, we suggested that the IGF-1/AKT signaling pathway affects the formation, growth, and movement of the adductor muscle in triploid oysters.

Promoter -202 A/C Polymorphism of Insulin-like Growth Factor Binding Protein-3 Gene and Non-small Cell Lung Cancer Risk (인슐린양 성장 인자 결합 단백-3 유전자 -202 좌위의 다형성에 따른 비소세포폐암의 위험도)

  • Moon, Jin Wook;Chang, Yoon Soo;Han, Chang Hoon;Kang, Shin Myung;Park, Moo Suk;Byun, Min Kwang;Chung, Wou Young;Park, Jae Jun;Yoo, Kyeong Nam;Shin, Ju Hye;Kim, Young Sam;Chang, Joon;Kim, Sung Kyu;Kim, Hee Jung;Kim, Se Kyu
    • Tuberculosis and Respiratory Diseases
    • /
    • v.58 no.4
    • /
    • pp.359-366
    • /
    • 2005
  • Background : IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of IGF by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from its degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Method : We attempted to ascertain whether A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects. Result : In the 104 NSCLC subjects, the genotypic frequencies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16). Conclusion : These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

Study on the diagnostic utility of serum levels of insulin-like growth Factor-I and insulin-like growth factor binding protein-3 in growth hormone deficiency (성장호르몬 결핍증 진단에 있어서 혈중 insulin-like growth factor-I 및 insulin-like growth factor binding protein-3 농도의 진단적 유용성에 대한 연구)

  • Ji, Geun Ha;Lee, Jeong Nyeo;Chung, Woo Yeong
    • Clinical and Experimental Pediatrics
    • /
    • v.51 no.12
    • /
    • pp.1329-1335
    • /
    • 2008
  • Purpose : This study aimed to determine the best cutoff line for insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to discriminate between growth hormone deficiency (GHD) patients and the control group. Methods : Two hundred thirty subjects with normal controls (129 boys and 101 girls, aged 7-15 years), 14 patients with complete GHD (12 boys and 2 girls), and 17 patients with partial GHD (9 boys and 8 girls) were studied. IGF-I serum concentrations were measured by radioimmunoassay (RI), and IGFBP-3 concentrations were measured by immunoradiometric assay (IRMA). Results : The receiver operating characteristic (ROC) plot analysis showed that the best IGF-I and IGFBP-3 cutoff line was at -1 standard deviation (SD). By comparing IGF-I serum levels of GHD children within 1 SD of normal control, we determined the sensitivity (S) (87.5-100%) and specificity (Sp) (80-84.6%) according to the age group. For IGFBP-3, we determined the following values: S (58.7-85.7%) and Sp (79.2-85.5%). Eleven of 14 patients with complete GHD (78.5%) and 16 of 17 patients with partial GHD (94.1%) had IGF-I concentrations equal to or below -1 SD of the control group mean. Ten of 12 complete GHD children (83.3%) and 13 of 17 partial GHD children (76.5%) had IGFBP-3 concentrations equal or below -1 SD of the control group mean. Conclusion : We conclude that the measurement of IGF-I and IGFBP-3 concentrations might provide essential supplementary data in the diagnostic evaluation of patients with GHD. Our results support the need to use cutoff lines based on below -1 SD of the control.

Insulin-like Growth Factor-1, IGF-binding Protein-3, C-peptide and Colorectal Cancer: a Case-control Study

  • Joshi, Pankaj;Joshi, Rakhi Kumari;Kim, Woo Jin;Lee, Sang-Ah
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.9
    • /
    • pp.3735-3740
    • /
    • 2015
  • Context: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). Objective: To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models. Materials and Methods: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models. Results: Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. Conclusions: The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.

The Endocrine Regulation of Chicken Growth

  • Kim, Jin-Wook
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.23 no.12
    • /
    • pp.1668-1676
    • /
    • 2010
  • The somatotropic axis plays a key role in proliferation and differentiation of avian organs during both pre- and posthatching periods. This review discusses the complexity of regulation of the endocrine system for chicken development and growth by growth hormone (GH), insulin-like growth factor (IGF), and IGF binding protein (IGFBP). In addition, the thyrotropic axis, including thyrotropin-releasing hormone (TRH) and thyroid hormones ($T_4$ and $T_3$), is also involved in the GH-secreting pattern. In mammals, IGFI and -II are always sequestered in a 150 kDa non-covalent ternary complex. This complex consists of one molecule each of IGF-I or IGF-II, IGFBP-3 or IGFBP-5 and an acid labile subunit (ALS). Chick ALS is identified in different strains for the first time, and further investigation of the expression of ALS on developmental stage and ALS effect on IGF bioavailability may be addressed in the future.

Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation

  • Lee, Dong Hyup;Kim, Jung Eun;Kang, Young Jin
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.17 no.2
    • /
    • pp.157-162
    • /
    • 2013
  • Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.

Identification of Novel SNPs in Bovine Insulin-like Growth Factor Binding Protein-3 (IGFBP3) Gene

  • Kim, J.Y.;Yoon, D.H.;Park, B.L.;Kim, L.H.;Na, K.J.;Choi, J.G.;Cho, C.Y.;Lee, H.K.;Chung, E.R.;Sang, B.C.;Cheong, I.J.;Oh, S.J.;Shin, Hyoung Doo
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.18 no.1
    • /
    • pp.3-7
    • /
    • 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.

Changes of insulin like growth factor-I, IGF-I carrier protein in streptozotocin-induced diabetic rat (Streptozotocin에 의해 유도된 당뇨쥐의 IGF-I, IGFBPs 및 IGF-I carrier protein의 변화)

  • Heo, Young-ran;Jin, Song-jun;Kim, Jin-shang;Kang, Chang-won
    • Korean Journal of Veterinary Research
    • /
    • v.40 no.3
    • /
    • pp.489-496
    • /
    • 2000
  • This study was conducted to investigate the effects of streptozotocin-induced (STZ) diabetes on insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBPs), and IGF-I carrier proteins in serum, liver, and kidney. The levels of total and free IGF-I were measured by radioimmunoassay (RIA). The patterns of IGFBPs were determined by western ligand blotting (WLB) analysis. The profiles of IGF-I carrier proteins in serum were determined by column chromatography. The levels of total and free IGF-I in serum were lower in STZ-induced diabetic rat than normal rat (p<0.01). Similarly, the levels of total IGF-I in liver was lowered in STZ-induced diabetic rats. On the other hand, the levels of total IGF-I in kidney were increased in STZ-induced diabetic rats compared with normal rats (p<0.01). In serum and liver from STZ-induced diabetic rats, the amount of IGFBP-3 was decreased and the amount of IGFBP-2 was increased compared with normal rats. There was a not difference in amount of IGFBP-4 in serum between STZ-induced diabetic rats and normal rats. The serums of normal rats have higher 150kDa carrier proteins than in STZ-induced diabetic rats, whereas, most of 50kDa carrier proteins were found in STZ-induced diabetic rats. These results demonstrate that in STZ-induced diabetic rats, IGF-I/IGFBPs system that included functional bioactivity was changed in serum as well as tissues, and these changes may play an important role in pathogenesis of diabetes.

  • PDF

Investigation of the Insulin-like Growth Factor System in Breast Muscle during Embryonic and Postnatal Development in Langshan and Arbor Acres Chickens Subjected to Different Feeding Regimens

  • Lu, F.Z.;Chen, J.;Wang, X.X.;Liu, Honglin
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.22 no.4
    • /
    • pp.471-482
    • /
    • 2009
  • Nutrient availability may control muscle growth directly and indirectly through its influence on regulatory factors. We analyzed the effects of nutrient availability on the breast muscle insulin-like growth factor system. Real time RT-PCR was used to quantify the level of transcription in breast muscle from Langshan (LS) layer and Arbor Acres (AA) broiler chickens subjected to different feeding regimens during embryonic and postnatal development. The AA chickens were fed AA diet (AA, control group) while the LS chickens were either fed LS diet (LL) or AA diet (LA). According to our results, insulin-like growth factor (IGF)-II (embryonic day 16 (E16) - postnatal day 42 (P42)), IGF-I receptor (IGF-IR, E18-P42), and IGF binding protein (IGFBP)-2 (E18-P42), -5 (E16-P14), -7 (E12-P0), and -3 (E12-P0) were positively correlated with IGF-I, while IGFBP-3 (P0-P28) was negatively correlated with IGF-I. In comparison, IGF-IR (E18-P42), IGFBP-2 (E18-P42), IGFBP-5 (E14-P0), and IGFBP-3 (E16-P0) were positively correlated with IGF-II, while IGF-IR (E10-E16) and IGFBP-3 (P0-P28) were negatively correlated with IGF-II. Moreover, IGFBP-2 (E16-P42), -7 (E10-E16), and -3 (E10-E16) were positively correlated with IGF-IR, while IGFBP-3 (P0-P28) was negatively correlated with IGF-IR. Finally, IGFBP-7 (E12-P0) was positively correlated with IGFBP-3, while IGFBP-2 (P0-P28) and -7 (P0-P42) were negatively correlated with IGFBP-3. Overall, the AA chickens exhibited higher levels of IGF-I, IGF-IR, and IGFBP-2 mRNA expression than the LL chickens, while the opposite was true for IGFBP-7. No strain differences in IGF-I, IGF-IR, and IGFBP-7 mRNA expression were detected between LA and AA chickens; however, a strain difference was observed for IGFBP-2. LA chickens exhibited higher levels of IGFBP-2 than LL chickens, while the opposite was true for IGFBP-7. Our data show the first evidence that certain genes may be correlated during specific developmental periods and that strain differences in the expression of those genes in LS and AA chickens are due to differential responses to the same diet.

Roles of the Insulin-like Growth Factor System in the Reproductive Function;Uterine Connection (Insulin-like Growth Factor Systems의 생식기능에서의 역할;자궁편)

  • Lee, Chul-Young
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.23 no.3
    • /
    • pp.247-268
    • /
    • 1996
  • It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.

  • PDF