Genomes and Genes
Gene Symbol: Igfbp3
Description: insulin-like growth factor binding protein 3
Alias: IGF-BP3, insulin-like growth factor-binding protein 3, IBP-3, IGF-binding protein 3, IGFBP-3, insulin-like growth factor-binding protein (IGF-BP3)
- Lee K, Cobb L, Paharkova Vatchkova V, Liu B, Milbrandt J, Cohen P. Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of IGFBP-3. Carcinogenesis. 2007;28:1653-8 pubmed..Taken together, our results verify an important role for the orphan nuclear receptor Nur77 in the apoptotic actions of IGFBP-3. ..
- Imai Y, Moralez A, Andag U, Clarke J, Busby W, Clemmons D. Substitutions for hydrophobic amino acids in the N-terminal domains of IGFBP-3 and -5 markedly reduce IGF-I binding and alter their biologic actions. J Biol Chem. 2000;275:18188-94 pubmed..The availability of these mutants will make it possible to determine if there are direct, non-IGF-I-dependent effects of IGFBP-3 and -5 on cellular physiologic processes in cell types that secrete IGF-I. ..
- Pilewski J, Liu L, Henry A, Knauer A, Feghali Bostwick C. Insulin-like growth factor binding proteins 3 and 5 are overexpressed in idiopathic pulmonary fibrosis and contribute to extracellular matrix deposition. Am J Pathol. 2005;166:399-407 pubmed..Taken together, our results suggest that IGFBPs play an important role in the development of fibrosis in IPF. ..
- Clemmons D, Moses A, Sommer A, Jacobson W, Rogol A, Sleevi M, et al. Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. Growth Horm IGF Res. 2005;15:265-74 pubmed..Coadministration of IGFBP-3 with IGF-I produces lower free IGF-I (Tmax and Cmax) levels compared to administration of IGF-I alone and is associated with relatively low incidence of side effects during 2 weeks of administration. ..
- Miller B, Khosravi M, Patterson M, Conover C. IGF system in children with congenital disorders of glycosylation. Clin Endocrinol (Oxf). 2009;70:892-7 pubmed publisher..Inadequate glycosylation of IGFBP-3 and ALS has a negative effect on the function of these proteins in vivo. This study provides the first evidence in humans for the importance of glycosylation on components of the IGF system. ..
- Walker G, MacLeod K, Williams A, Cameron D, Smyth J, Langdon S. Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clin Cancer Res. 2007;13:1438-44 pubmed..Quantitative reverse transcription-PCR analysis showed that IGFBP3 and IGFBP5 were down-regulated and IGFBP4 was up-regulated by 17beta-estradiol (E(2)) in an estrogen receptor (ER)-..
- Beeton C, Brooks R, Chatfield D, Human M, Rushton N. Circulating levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in patients with severe head injury. J Bone Joint Surg Br. 2002;84:434-9 pubmed..These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury. ..
- Grzelkowska Kowalczyk K, Wieteska W. Changes of insulin-mediated protein kinases phosphorylation and the expression of IGFBP-3 in skeletal muscle of streptozotocin-diabetic mice. Pol J Vet Sci. 2005;8:231-40 pubmed
- Rajah R, Lee K, Cohen P. Insulin-like growth factor binding protein-3 mediates tumor necrosis factor-alpha-induced apoptosis: role of Bcl-2 phosphorylation. Cell Growth Differ. 2002;13:163-71 pubmed..These findings confirm that IGFBP-3 is essential for TNF-alpha-induced apoptosis in PC-3 cells and that this IGFBP-3 effect includes the inactivation of Bcl-2 through serine phosphorylation. ..
- Narusawa K, Nakamura T, Suzuki K, Matsuoka Y, Lee L, Tanaka H, et al. The effects of recombinant human insulin-like growth factor (rhIGF)-1 and rhIGF-1/IGF binding protein-3 administration on rat osteopenia induced by ovariectomy with concomitant bilateral sciatic neurectomy. J Bone Miner Res. 1995;10:1853-64 pubmed..The action of rhIGF-1/IGFBP-3 on trabecular bone appeared to depend not only on the dose but also on the frequency of administration and the parts of the skeleton in rats. ..
- Lu Y, Liu X, Li S. [Effects of L-arginine on the expression of insulin-like growth factors and insulin-like growth factor binding protein 3 in rats with intrauterine growth retardation]. Zhongguo Dang Dai Er Ke Za Zhi. 2006;8:319-22 pubmed..the effects of L-arginine on the expression of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-3(IGFBP3)and IGF-I mRNA in brains of IUGR rats and the possible mechanisms of L-arginine...
- Ulmer A, Tabea Tauer J, Glauche I, Jung R, Suttorp M. TK inhibitor treatment disrupts growth hormone axis: clinical observations in children with CML and experimental data from a juvenile animal model. Klin Padiatr. 2013;225:120-6 pubmed publisher..A juvenile rat model predicts this side effect for dasatinib and bosutinib. Thus, growth and GH- related parameters should be monitored regularly in pediatric patients with CML on TKIs. ..
- Shimasaki S, Koba A, Mercado M, Shimonaka M, Ling N. Complementary DNA structure of the high molecular weight rat insulin-like growth factor binding protein (IGF-BP3) and tissue distribution of its mRNA. Biochem Biophys Res Commun. 1989;165:907-12 pubmed..6 kb band in liver, kidney, stomach, heart, adrenal, ovary, testis, spleen, lung, small and large intestine in varying amounts, but the message is below the limit of detection in hypothalamus and brain cortex. ..
- Huynh H, Alpert L, Alaoui Jamali M, Ng C, Chan T. Co-administration of finasteride and the pure anti-oestrogen ICI 182,780 act synergistically in modulating the IGF system in rat prostate. J Endocrinol. 2001;171:109-18 pubmed..These observations support a potential use of ICI in conjunction with finasteride in the prevention and/or treatment of prostate cancer. ..
- Palau N, Rebuffat S, Altirriba J, Piquer S, Hanzu F, Gomis R, et al. Role of IGFBP-3 in the regulation of ?-cell mass during obesity: adipose tissue/?-cell cross talk. Endocrinology. 2012;153:177-87 pubmed publisher..Of all the differentially expressed proteins, only the secreted ones were studied. IGF binding protein 3 (Igfbp3) was identified as the candidate for this effect...
- Wilczak N, Ramsaransing G, Mostert J, Chesik D, De Keyser J. Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis. Mult Scler. 2005;11:13-5 pubmed..However, there was a significant correlation (P =0.005) between IGFBP-3 serum levels and both the progression index of disability and the Multiple Sclerosis Severity Score in patients with primary progressive MS. ..
- Collett Solberg P, Fleenor D, Schultz W, Ware R. Short stature in children with sickle cell anemia correlates with alterations in the IGF-I axis. J Pediatr Endocrinol Metab. 2007;20:211-8 pubmed..028). We demonstrated that children with SCA have abnormalities in the IGF-I axis, which worsen with age. ..
- Albiston A, Herington A. Cloning and characterization of the growth hormone-dependent insulin-like growth factor binding protein (IGFBP-3) in the rat. Biochem Biophys Res Commun. 1990;166:892-7 pubmed
- Siahpush S, Vaughan T, Lampe J, Freeman R, Lewis S, Odze R, et al. Longitudinal study of insulin-like growth factor, insulin-like growth factor binding protein-3, and their polymorphisms: risk of neoplastic progression in Barrett's esophagus. Cancer Epidemiol Biomarkers Prev. 2007;16:2387-95 pubmed..Our findings, although based on a relatively small number of outcomes and subject to several limitations, indicate a potential role of the complex IGF system in neoplastic progression among persons with Barrett's esophagus. ..
- Ozen M, Cokugras H, Ozen N, Camcioglu Y, Akcakaya N. Relation between serum Insulin-like growth factor-I and insulin-like growth factor-binding protein-3 levels, clinical status and growth parameters in prepubertal cystic fibrosis patients. Pediatr Int. 2004;46:429-35 pubmed..Growth parameters of Turkish prepubertal CF patients are not markedly below national standards. Different genetic backgrounds of relevant populations certainly play an important role for the variable clinical course. ..
- Priego T, Ibanez de Caceres I, Martin A, Villanua M, Lopez Calderon A. Hepatic insulin-like growth factor-I binding protein 3 gene expression in rats with endotoxic shock: the role of glucocorticoids. Ann N Y Acad Sci. 2002;973:88-90 pubmed..These data suggest that the decrease in hepatic IGFBP-3 gene expression induced by LPS is not mediated by glucocorticoids. ..
- Duan C, Xu Q. Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions. Gen Comp Endocrinol. 2005;142:44-52 pubmed..In this article, we provide a brief overview of our current understanding of the IGF signaling system with particular reference to IGFBPs. ..
- Serrano M, Sanchez Gomez M, Bravo M. Insulin-like growth factor system gene expression in cervical scrapes from women with squamous intraepithelial lesions and cervical cancer. Growth Horm IGF Res. 2007;17:492-9 pubmed..The aim of this study was to evaluate the expression levels of IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and IGF-I receptor (IGF-IR) in exfoliated cervical cells in cervical carcinogenesis...
- Koklu E, Kurtoglu S, Akcakus M, Yikilmaz A, Gunes T. Serum insulin-like growth factor-I (IGF-I) IGF binding protein-3 (IGFBP-3) and leptin levels are related to abdominal aortic intima-media thickness in macrosomic newborns. Growth Horm IGF Res. 2007;17:26-32 pubmed..It might be speculated that these changes may exaggerate the atherosclerotic process later in life. ..
- O Rear L, Longobardi L, Torello M, Law B, Moses H, Chiarelli F, et al. Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-(beta) in mesenchymal chondroprogenitor cell growth. J Mol Endocrinol. 2005;34:723-37 pubmed..Collectively, these results demonstrate cross-talk between the IGFBP-3-dependent STAT-1 signaling and the TGF-beta-dependent ERK pathway that regulates MCC proliferation. ..
- Kurtoglu S, Ozturk M, Koklu E, Gunes T, Akcakus M, Hatipoglu N. Serum insulin-like growth factor-I (IGF-I), IGF-binding protein-3, and growth hormone levels in collodion babies: a case-control study. J Pediatr Endocrinol Metab. 2008;21:689-94 pubmed..567, p <0.001) and IGFBP-3 (r = -0.444, p = 0.003). Collodion babies had lower serum IGF-I and IGFBP-3 levels but higher serum GH levels than controls in the present case-control study. The underlying mechanism needs to be explored. ..
- Baker Méio M, Lopes Moreira M, Sichieri R, Moura A. Reduction of IGF-binding protein-3 as a potential marker of intra-uterine growth restriction. J Perinat Med. 2009;37:689-93 pubmed publisher..0001). In contrast, no associations were found between IGF-I serum levels and these anthropometric measurements. Our data show that SGA babies have significantly reduced IGFBP-3 concentrations at birth. ..
- Gravholt C, Chen J, Oxvig C, Overgaard M, Christiansen J, Frystyk J, et al. The GH-IGF-IGFBP axis is changed in Turner syndrome: partial normalization by HRT. Growth Horm IGF Res. 2006;16:332-9 pubmed..A sex hormone-dependent IGFBP-3 proteolytic activity (serine protease) leads to destabilization of the 150 kDa IGFBP-3 ternary complex in TS. During HRT both IGFBP-3 proteolytic activity and ternary complex formation is normalized. ..
- Boes M, Dake B, Booth B, Sandra A, Bateman M, Knudtson K, et al. IGF-I and IGFBP-3 transport in the rat heart. Am J Physiol Endocrinol Metab. 2003;284:E237-9 pubmed..This also suggests a novel and plausible mechanism whereby circulating IGFs reach sites of IGF bioactivity. ..
- Pu X, Wen A, Liu J, Zheng X, Xiao H, Xu Z, et al. shRNA constructs targeting IGFBP-3 alleviate age related erectile dysfunction in the rat. J Urol. 2014;192:990-6 pubmed publisher..The therapy may modulate smooth muscle integrity and increase the cGMP concentration. This may be a new direction for treating erectile dysfunction in clinical practice. ..
- Frystyk J, Grønbaek H, Skjaerbaek C, Flyvbjerg A, Orskov H, Baxter R. Developmental changes in serum levels of free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and the acid-labile subunit in rats. Endocrinology. 1998;139:4286-92 pubmed..However, in humans the adult level of fIGF-I rarely exceeds 0.3 nmol/liter, and IGFBP-1 usually circulates in excess of fIGF-I. Thus, our results also imply species differences in the IGF systems of humans and rats. ..
- Ajo R, Cacicedo L, Navarro C, Sanchez Franco F. Growth hormone action on proliferation and differentiation of cerebral cortical cells from fetal rat. Endocrinology. 2003;144:1086-97 pubmed..GH-induced IGFBP-3 may also have a role in these responses. Therefore, GH is able to activate the IGF-I/IGFBP-3 system in these cerebral cells and induce a physiological action of IGF-I. ..
- Zhou Z, Li F, Cheng S, Huang H, Peng B, Wang J, et al. Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated decreased testosterone concentrations in diabetic rats. Med Sci Monit. 2015;21:94-9 pubmed publisher..01). These results suggest that IGFBP-3 shRNA may rehabilitate erectile function via increases of concentrations of serum testosterone and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats. ..
- Spangenburg E, Abraha T, Childs T, Pattison J, Booth F. Skeletal muscle IGF-binding protein-3 and -5 expressions are age, muscle, and load dependent. Am J Physiol Endocrinol Metab. 2003;284:E340-50 pubmed
- Twigg S, Baxter R. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 1998;273:6074-9 pubmed..The demonstration of IGFBP-5-containing ternary complexes indicates an unrecognized form of IGF transport in the circulation and an additional mechanism for regulating IGF bioavailability. ..
- Ning Y, Schuller A, Bradshaw S, Rotwein P, Ludwig T, Frystyk J, et al. Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Mol Endocrinol. 2006;20:2173-86 pubmed
- Beattie J, Kreiner M, Allan G, Flint D, Domingues D, van der Walle C. IGFBP-3 and IGFBP-5 associate with the cell binding domain (CBD) of fibronectin. Biochem Biophys Res Commun. 2009;381:572-6 pubmed publisher..Using site-directed mutagenesis of (9-10)FNIII, we show both the "synergy" and RGD sites within these FN domains are required for maximum binding of both IGFBPs. We discuss the possible biological consequences of our results. ..
- Muhlbradt E, Asatiani E, Ortner E, Wang A, Gelmann E. NKX3.1 activates expression of insulin-like growth factor binding protein-3 to mediate insulin-like growth factor-I signaling and cell proliferation. Cancer Res. 2009;69:2615-22 pubmed publisher..Thus, there is a close relationship in vitro and in vivo between NKX3.1 and IGFBP-3. The growth-suppressive effects of NKX3.1 in prostate cells are mediated, in part, by activation of IGFBP-3 expression. ..
- Börzsönyi B, Demendi C, Nagy Z, Toth K, Csanád M, Pajor A, et al. Gene expression patterns of insulin-like growth factor 1, insulin-like growth factor 2 and insulin-like growth factor binding protein 3 in human placenta from pregnancies with intrauterine growth restriction. J Perinat Med. 2011;39:701-7 pubmed publisher..Insulin and carbohydrate metabolism are also impaired in IUGR fetuses. In the placentas from pregnancies with IUGR, IGF-2 is overexpressed reflecting its physiological role in optimizing energy distribution in a low-energy environment. ..
- Völkl T, Rauh M, Schofl C, Dörr H. IGF-I-IGFBP-3-acid-labile subunit (ALS) complex in children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). Growth Horm IGF Res. 2011;21:191-8 pubmed publisher..Our data provide evidence that the components of the trimeric IGF-I-IGFBP-3-ALS complex are altered in CAH children with possible implications on pubertal growth and final height. ..
- Albiston A, Saffery R, Herington A. Cloning and characterization of the promoter for the rat insulin-like growth factor-binding protein-3 gene. Endocrinology. 1995;136:696-704 pubmed..These data indicate that suitable transfected cell systems can be established in which additional investigations can be undertaken into the mechanisms of cell- and species-specific hormonal regulation of IGFBP-3 gene expression. ..
- Villafuerte B, Zhang W, Phillips L. Insulin and insulin-like growth factor-I regulate hepatic insulin-like growth factor binding protein-3 by different mechanisms. Mol Endocrinol. 1996;10:622-30 pubmed
- Chan K, Spencer E. Megakaryocytes endocytose insulin-like growth factor (IGF) I and IGF-binding protein-3: a novel mechanism directing them into alpha granules of platelets. Endocrinology. 1998;139:559-65 pubmed..As reverse transcription-PCR has shown that the IGF-I, but not the IGFBP-3, gene is expressed by megakaryocytes, there may be two mechanisms for directing IGF-I into the alpha-granules of platelets. ..
- Jeschke M, Herndon D, Barrow R. Insulin-like growth factor I in combination with insulin-like growth factor binding protein 3 affects the hepatic acute phase response and hepatic morphology in thermally injured rats. Ann Surg. 2000;231:408-16 pubmed..IGF-I/BP-3 attenuates the hypermetabolic response after thermal injury and may improve the clinical outcome. ..
- Geyer M, Grassel S, Straub R, Schett G, Dinser R, Grifka J, et al. Differential transcriptome analysis of intraarticular lesional vs intact cartilage reveals new candidate genes in osteoarthritis pathophysiology. Osteoarthritis Cartilage. 2009;17:328-35 pubmed publisher..In addition, this study also revealed novel genes not yet reported to play a role in the pathophysiology of joint destruction in OA. ..
- Chuang S, Patton K, Schafernak K, Papavero V, Lin F, Baxter R, et al. Over expression of insulin-like growth factor binding protein 3 in clear cell renal cell carcinoma. J Urol. 2008;179:445-9 pubmed..With a combination of cDNA microarrays, Western blot and immunohistochemistry we confirmed that IGFBP-3 is a marker for clear cell renal cell carcinoma. Furthermore, higher IGFBP-3 expression was associated with higher Fuhrman grade. ..
- Hinz S, Kempkensteffen C, Weikert S, Schostak M, Schrader M, Miller K, et al. EZH2 polycomb transcriptional repressor expression correlates with methylation of the APAF-1 gene in superficial transitional cell carcinoma of the bladder. Tumour Biol. 2007;28:151-7 pubmed..Moreover, these data present first evidence that APAF-1 methylation is related to transcriptional activity of EZH2 expression in early-stage tumor disease of the bladder. ..
- Vasylyeva T, Chen X, Ferry R. Insulin-like growth factor binding protein-3 mediates cytokine-induced mesangial cell apoptosis. Growth Horm IGF Res. 2005;15:207-14 pubmed..In summary, these data support a novel mechanism for TNF-alpha-induced mesangial cell apoptosis mediated by IGFBP-3 and present regulation of pThr308 activity as a novel mechanism underlying IGFBP-3 action. ..
- Priego T, Granado M, Martín A, López Calderón A, Villanúa M. Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats. J Endocrinol. 2005;185:467-76 pubmed
- Oh J, Wu W, Tortolero Luna G, Broaddus R, Gershenson D, Burke T, et al. Increased plasma levels of insulin-like growth factor 2 and insulin-like growth factor binding protein 3 are associated with endometrial cancer risk. Cancer Epidemiol Biomarkers Prev. 2004;13:748-52 pubmed..the association of IGFs and endometrial cancer risk, we measured the plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with endometrial cancer and 80 age-matched control subjects with no history ..