Disease relevance of IGFBP1

• When transplant recipients with and without posttransplant erythrocytosis were compared, similar levels of IGF-I were found; however, the group with erythrocytosis had significantly elevated IGFBP1 and IGFBP3 [1].
• However, placenta weight and the placenta weight to birth weight percentage were negatively correlated with AF IGF-I, IGF-II, and IGFBP1; placenta weight to birth weight percentage was lower in pregnancies with IGFBP1 values more than the 50th percentile compared with those less than or equal to the 50th percentile at sampling [2].
• Our results suggest that IGFBP1 and Follistatin-like 3 are highly up-regulated in IUGR in the placenta [3].
• In this study, we performed expression profiling of all six human IGFBP genes in prostate and bone cancer cells and demonstrated that IGFBP1, 3 and 5 are primary 1alpha,25(OH)2D3 target genes [4].
• PURPOSE: We conducted this study to fully characterize the expression and hormonal regulation of IGF-binding protein expression in human MCF-7 breast cancer cells and to test the ability of purified IGFBP-1 to inhibit IGF-I action [5].

Psychiatry related information on IGFBP1

• The possible effect of physical activity on IGFBP-1 requires further investigation [6].
• The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa [7].
• IGFBP-1 is elevated in the blood as a result of sepsis, AIDS, excessive alcohol consumption, and diabetes and may, in part, be responsible for the wasting observed during these pathophysiological conditions [8].
• It is well known that chronic alcohol abuse impairs liver function, but less is known about how an acute intake of moderate quantities of alcohol affects hepatic production of IGF-1 and IGFBP-1 [9].
• This study examined the hypothesis that sustained physical activity and sleep deprivation superimposed on a short-term energy deficit would alter the IGFBP concentrations and alter the proportions of IGF-I circulating in ternary vs. binary molecular complexes [10].

High impact information on IGFBP1

• IGFBP-1 interacts with alpha(5)beta(1) integrin, influencing cell adhesion and migration [11].
• In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal [12].
• Use of mutagenesis to probe IGF-binding protein structure/function relationships [13].
• Over the course of evolution, some members evolved into high-affinity IGF binders and others into low-affinity IGF binders, thereby conferring on the IGFBP superfamily the ability to influence cell growth by both IGF-dependent and IGF-independent means (Fig. 10) [14].
• For example, the similarity of the IGFBP C terminus to the thyroglobulin type-I domain shows that the IGFBPs are also structurally related to numerous other proteins carrying the same domain (87) [14].

Chemical compound and disease context of IGFBP1

• Hyperinsulinemia, increased early insulin responses to glucose, increased glucose uptake rate in peripheral tissues, elevated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood [15].
• We have systematically investigated the binding contribution of each IGF-I amino acid side chain toward IGFBP-1 and IGFBP-3, combining alanine-scanning mutagenesis and monovalent phage display [16].
• IGFBP-1 has been shown to inhibit somatic linear growth, weight gain, tissue growth, and glucose metabolism [17].
• Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells [18].
• We examined whether the concentrations of estrone, E2, IGF-I, IGF-II, and IGF-binding protein-1 (IGFBP-1), -2, and -3 in umbilical cord blood plasma differed in female neonates of three racial/ethnic groups with contrasting breast cancer risk [19].

Biological context of IGFBP1

• Genetic variation at the IGF2 and IGFBP1 loci could be among the factors responsible for the inter-individual differences observed in the response to long-term alterations in energy balance and should be further investigated in larger cohorts [20].
• As a consequence of this event, the entire IGL locus, less the first three Vlambda elements, is translocated to chromosome 7, whereas the three remaining Vlambda elements on the der(22) are juxtaposed with IGFBP3 and IGFBP1 [21].
• After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester [2].
• Using the chromatin immunoprecipitation technique, we demonstrated that liganded PGR was recruited to the IGFBP1 promoter region (-358 to -49) [22].
• When FOXO1A expression was silenced using small interference RNA, IGFBP1 expression decreased in both HuF and HEC-1B cells [22].

Anatomical context of IGFBP1

• The subjects with IGFBP1 Bgl II AA (n = 8) showed greater increases in abdominal visceral fat (p < 0.01), OGTT insulin area (p = 0.05) and total cholesterol (p < 0.03) with overfeeding than the subjects with AG + GG (n = 16) [20].
• Insulin-like growth factor-binding protein-1 (IGFBP1) is a major secretory product of the decidualized endometrium [22].
• Fetal hepatocytes secreted three IGF-binding proteins (IGFBPs), including IGFBP1, but not IGFBP3. hGH did not alter fetal hepatocyte IGFBPs but stimulated glucose uptake [23].
• The expressions of the IGFBP1 and Follistatin-like 3 genes in four single IUGR and four AGA placentas were also examined by RT-PCR [3].
• Oligodendrocytes in normal-appearing white matter expressed only IGFBP1, not IGFs or IGF-IR [24].

Associations of IGFBP1 with chemical compounds

• Insulin-like growth factor 2 (IGF2 ) and IGF-binding protein 1 (IGFBP1) gene variants are associated with overfeeding-induced metabolic changes [20].
• In addition, pretreatment of ES cells with mepacrine decreased PRL/IGFBP1 expression and inhibited morphological change, whereas pretreatment with propranolol caused no changes, as compared to cAMP-treated cells, which suggests that PA induces decidualization through phospholipase A2 (PLA2G1B) [25].
• On the other hand, the secretion of IGFBP1 was greatly stimulated by P and R [26].
• Estrogen also increased IGFBP production, making it unlikely that the IGFBPs induced by estrogen in MCF-7 cells could function as major inhibitors of IGF action [5].
• Moreover, from alignment of the predicted protein sequences of IGFBP-1 and IGFBP-2, extensive conservation of the distribution of cysteine residues is observed [27].
• Individuals in the highest quartile at baseline for an algorithm incorporating fasting IGFBP-1, blood glucose, proinsulin and waist and height had a 40-fold increased risk of developing type 2 diabetes compared with the lowest quartile (95% CI 7.7-214) [28].

Physical interactions of IGFBP1

• Western ligand blotting of column effluent samples revealed 37-/43-kDa IGFBP-3 primarily in the 150-kDa complex in serum and a marked reduction in the amount of the 37-/43-kDa IGFBP in PF [29].
• In conclusion, mac25 specifically binds IGFs and constitutes a new member of the IGFBP family, IGFBP-7 [30].
• We show here that tIGF-I, a non-IGFBP-binding analogue of IGF-1, is a more potent mitogenic stimulator of the keratinocyte cell line HaCaT than IGF-I, suggesting that keratinocytes produce IGFBPs that modulate their response to IGF-I [31].
• All members of the IGFBP family bind IGF-I and IGF-II with about equal affinity [32].
• IGFBP-2 is a form of binding protein that is structurally distinct from IGFBP-1 [33].

Enzymatic interactions of IGFBP1

• Levels of proteolytic activity directed against insulin-like growth factor binding protein 3 (IGFBP-3) and the distribution of phosphorylated isoforms of IGFBP-1 were assessed in matched sample sets of maternal serum, coelomic fluid and amniotic fluid from 21 pregnancies at 6-12 weeks gestation [34].
• MMP-26 cleaved Phe(352)-Leu(353) and Pro(357)-Met(358) in the reactive loop of alpha(1)-proteinase inhibitor and His(140)-Val(141) in insulin-like growth factor-binding protein-1, probably rendering these substrates inactive [35].
• In vitro and in situ experiments demonstrated that PAPP-A cleaves insulin-like growth factor-binding protein (IGFBP)-2, but not IGFBP-3, in the conditioned medium of C2C12 myoblasts [36].
• Tg localized in fibroblast membranes was also shown to catalyze the formation of native IGFBP-1 multimers, however, Q66A/Q67A IGFBP-1 failed to polymerize [37].
• Furthermore, IGFBP-1 was phosphorylated by purified casein kinase I and casein kinase II at sites phosphorylated by the peak I and II kinases [38].

Co-localisations of IGFBP1

• This IGFBP co-migrated with a pure IGFBP-3 standard [39].

Regulatory relationships of IGFBP1

• The mitogenic effect of IGF-1 was enhanced by IGFBP-1 in both cell types [40].
• These results indicate that IGF-I and IGF-II induce an IGFBP that is different from previously characterized human IGFBPs [41].
• These studies show that FKHR and HOXA10 interact directly and can function cooperatively to stimulate IGFBP-1 promoter activity in endometrial cells and perhaps in other settings [42].
• All IGFBP-secreting cell lines expressed the IGFBP-2 gene as determined by Northern blot analysis [43].
• IGFBP-1 was expressed only in the hepatocytes and IGFBP-3 mRNA was modestly expressed within the kidney (developing nephrons, collecting system mesenchyme), and liver (hepatocytes) [44].

Other interactions of IGFBP1

• The Mr 32,000 binding protein is similar in size to IGFB-1 and different from IGFBP-2 and IGFBP-3, but it does not cross-react with an antibody against IGFBP-1 [45].
• This IGFBP (HT29-IGFBP) has been characterized by performing ligand blotting and competitive binding experiments [46].
• The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry [47].
• Thus, in adult chronic renal failure, reducing protein intake by 40% did not modify the growth hormone/IGF-1/IGFBP axis [48].
• Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study [49].

Analytical, diagnostic and therapeutic context of IGFBP1

• After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1+/-4.1 vs 30.2+/-5.3, 31.9+/-5.1 g/L), prealbumin (79.6+/-28.0 vs 106.6+/-54.4, 108.4+/-55.0 g/L), cholesterol (76.3+/-16.7 vs 85.6+/-32.3, 96.1+/-38.7 mg/dL), and IGFBP1 (56.8+/-47.2 vs 89.7+/-50.3 ng/mL after 2 wk) were significantly increased compared to control group (P<0.05) [50].
• Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA [50].
• CONCLUSIONS: Findings showed that reduced expression of genes related to cell invasion and immunosuppression, especially FTL and IGFBP1, were associated with development of GTN, and this finding may provide a better understanding of the pathogenesis of GTN [51].
• We have mapped and regionally localized the genes coding for human IGFBP1, 2, 3, and 4, by in situ hybridization and somatic cell hybrid analysis [52].
• RESULTS: IGFBP-1 gene expression was detected by Northern blot analysis in one NSCLC cell line only [53].

References