* 146730

INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 1; IGFBP1


Alternative titles; symbols

IBP1
PLACENTAL PROTEIN 12
IGF-BP25


HGNC Approved Gene Symbol: IGFBP1

Cytogenetic location: 7p12.3     Genomic coordinates (GRCh38): 7:45,888,488-45,893,660 (from NCBI)


TEXT

Description

Unlike insulin, both IGF I (147440) and IGF II (147470) circulate in plasma tightly bound to specific binding proteins. Two major forms of IGF-binding proteins have been identified in human plasma, a low molecular weight form and a high molecular weight form. The low molecular weight IGF-binding protein (IGFBP1) is synthesized in liver, secretory endometrium, and decidua. It binds both IGF I and IGF II with high affinity.


Cloning and Expression

Brinkman et al. (1988) cloned and sequenced a cDNA encoding a low molecular weight IGF-binding protein from a human placenta cDNA library. Expression of the cDNA encoding what they termed 'IBP-1' in monkey COS cells resulted in the synthesis of a 30-kD protein that binds IGF I and is immunologically indistinguishable from the IGF-binding protein isolated from amniotic fluid or human serum. Northern blotting analysis demonstrated that expression of the IBP1 gene is limited to placental membranes and fetal liver.

Brewer et al. (1988) purified an insulin-like growth factor-binding protein from human amniotic fluid and showed that it potentiates the effects of IGF I in vitro. They used a polyclonal antibody to this protein to isolate a cDNA clone from a human decidua library. They found that the clone encodes a polypeptide of 28,832 Da that includes sequences of 9 tryptic peptides that had been prepared from the purified protein. The protein has 15 cysteines clustered at the amino and carboxy ends of the molecule. Near its C terminus the protein has an RGD sequence (arginine-glycine-aspartic acid) which may account for its ability to attach to cells and to potentiate the biologic actions of IGF I.


Nomenclature

IGFBP1 is also known as amniotic fluid binding protein (AFBP), placental protein-12, alpha-pregnancy-associated endometrial globulin, growth hormone independent-binding protein, binding protein-28, binding protein-26, and binding protein-25 (Ballard et al., 1990).


Gene Structure

Brinkman et al. (1988) found that the IGFBP1 gene has 4 exons and spans 5.9 kb.


Mapping

Brinkman et al. (1988) mapped the IGFBP1 gene to chromosome 7 by Southern analysis of genomic DNA isolated from human-rodent somatic cell hybrids.

Alitalo et al. (1989) localized the IGFBP1 gene to 7p13-p12 by in situ hybridization. Ekstrand et al. (1990) confirmed this assignment by Southern analysis of somatic hybrid cell DNA and by in situ hybridization. Alitalo et al. (1989) described a 2-allele RFLP with allele frequencies that made it useful as a genetic marker for the proximal short arm of chromosome 7.


Gene Function

IGFBP1 is elevated in the fetal circulation of human and animal pregnancies complicated by intrauterine growth retardation (IUGR) caused by placental insufficiency and in utero hypoxia and is believed to restrict fetal growth by sequestering IGFs. Popovici et al. (2001) established highly pure primary cultures of human fetal hepatocytes in vitro and investigated the expression of IGFBP1 and the effects of hypoxia on expression of IGFBP1 mRNA and protein. Hepatocytes were cultured in defined medium, and Northern blot analysis revealed expression of a 1.5-kb IGFBP1 mRNA transcript in hepatocytes cultured under normoxic conditions for 24 hours that did not increase in steady-state levels after 48 hours in culture. Under hypoxic conditions, IGFBP1 mRNA expression increased 3- to 4-fold compared with normoxic controls. Western blot analysis of conditioned medium revealed the presence of IGFBP1, IGFBP2 (146731), IGFBP3 (146732), and IGFBP4 (146733). IGFBP1 was the most abundant IGFBP in conditioned medium, and densitometric analysis revealed a 2.5-fold increase in IGFBP1 under hypoxic, compared with normoxic, conditions, supporting the immunoradiometric assay results. A 3-fold increase in IGFBP3 mRNA, but not other IGFBPs, was noted under hypoxic, compared with normoxic, conditions. The authors concluded that hypoxia upregulates fetal hepatocyte IGFBP1 mRNA steady-state levels and protein, with this being the major IGFBP derived from the fetal hepatocyte. These data also supported a role for the fetal liver as a source of elevated circulating levels of IGFBP1 in fetuses with in utero hypoxia and IUGR.

Using loss- and gain-of-function approaches with zebrafish embryos, Kajimura et al. (2005) demonstrated that Igfbp1 mediated hypoxia-induced embryonic growth retardation and developmental delay. When tested in vitro with cultured zebrafish embryonic cells, Igfbp1 itself had no mitogenic activity, but it inhibited Igf1- and Igf2-stimulated cell proliferation by binding to and inhibiting the activities of IGFs.

In a study comparing the binding of transcriptional regulators to promoter regions across species (human and mouse), Odom et al. (2007) demonstrated that the binding site for HNF6 (604164) in the human IGFBP1 gene is in the promoter region, while that in the mouse Igfbp1 gene is in the first intron.

Liver is generally refractory to apoptosis induced by p53 (TP53; 191170). Leu and George (2007) found that p53 activation led to enhanced expression of IGFBP1 in human hepatoma cells. A portion of intracellular IGFBP1 localized to mitochondria, where it bound the proapoptotic protein BAK (BAK1; 600516). Binding of IGFBP1 to BAK impaired formation of the proapoptotic p53/BAK complex and induction of apoptosis in cultured human and mouse cells and in mouse liver. In contrast, livers of Igfbp1-deficient mice exhibited spontaneous apoptosis accompanied by p53 mitochondrial accumulation and evidence of Bak oligomerization. Leu and George (2007) concluded that IGFBP1 is a negative regulator of the p53/BAK-dependent pathway of apoptosis.


Animal Model

Leu et al. (2003) treated Igfbp1 -/- mice with a normally sublethal dose of Fas agonist. The mice developed massive hepatocyte apoptosis and caspase activation within 3 hours of treatment. Earlier (0.5-1 hour after treatment), Igfbp1-deficient livers had enhanced signaling via the integrin receptor and elevated activated matrix metalloproteinase-9 (MMP9; 120361), a known target of fibronectin signaling and activator of TGF-beta (see TGFB1; 190180). Within 3 hours of treatment, there was elevated expression of active TGFB1, a hepatocyte apoptogen, which correlated with the appearance of the apoptotic process. Igfbp1 -/- mice that were treated with IGFBP1 prior to treatment with Fas agonist were protected against lethality and Fas-mediated apoptotic injury. IGFBP1 treatment suppressed the expression of both MMP9 and TGFB1, supporting their role in the apoptotic process. Igfbp1 -/- mice also displayed increased injury in a toxic hepatic injury model caused by CCl4. Leu et al. (2003) suggested that IGFBP1 may function as a critical survival factor in the liver by suppressing the level and activation of specific proapoptotic factors via its regulation of integrin-mediated signaling.

Experiments with rats indicated that Igfbp1 is one of the most rapidly and highly induced genes in regenerating liver following partial hepatectomy. Leu et al. (2003) found that Igfbp1-null mice developed normally, but liver regeneration after partial hepatectomy was abnormal and was characterized by liver necrosis and reduced and delayed hepatocyte DNA synthesis. The activation of p42 Mapk (176948) and p44 Mapk (601795) and induction of C/EBP-beta (189965) was abnormally reduced following hepatectomy. Cell cycle abnormalities were similar to those observed in hepatectomized C/EBP-beta-null mice in that cyclin A1 (604036) and cyclin B1 (123836) expression was delayed and reduced, whereas cyclin D1 (168461) expression was normal.


REFERENCES

  1. Alitalo, T., Kontula, K., Koistinen, R., Aalto-Setala, K., Julkunen, M., Janne, O. A., Seppala, M., de la Chapelle, A. The gene encoding human low-molecular weight insulin-like growth-factor binding protein (IGF-BP25): regional localization to 7p12-p13 and description of a DNA polymorphism. Hum. Genet. 83: 335-338, 1989. [PubMed: 2478445, related citations] [Full Text]

  2. Ballard, F. J., Baxter, R. C., Binoux, M., Clemmons, D. R., Drop, S. L. S., Hall, K., Hintz, R. L., Rechler, M. M., Rutanen, E. M., Schwander, J. C. Report on the nomenclature of the IGF binding proteins. J. Clin. Endocr. Metab. 70: 817-818, 1990.

  3. Brewer, M. T., Stetler, G. L., Squires, C. H., Thompson, R. C., Busby, W. H., Clemmons, D. R. Cloning, characterization, and expression of a human insulin-like growth factor binding protein. Biochem. Biophys. Res. Commun. 152: 1289-1297, 1988. Note: Erratum: Biochem. Biophys. Res. Commun. 155: 1485 only, 1988. [PubMed: 2454104, related citations] [Full Text]

  4. Brinkman, A., Groffen, C. A. H., Kortleve, D. J., Drop, S. L. S. Organization of the gene encoding the insulin-like growth factor binding protein IBP-1. Biochem. Biophys. Res. Commun. 157: 898-907, 1988. [PubMed: 2849945, related citations] [Full Text]

  5. Brinkman, A., Groffen, C., Kortleve, D. J., Geurts van Kessel, A., Drop, S. L. S. Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1). EMBO J. 7: 2417-2423, 1988. [PubMed: 2461294, related citations] [Full Text]

  6. Ekstrand, J., Ehrenborg, E., Stern, I., Stellan, B., Zech, L., Luthman, H. The gene for insulin-like growth factor binding protein-1 is localized to human chromosomal region 7p14-p12. Genomics 6: 413-418, 1990. [PubMed: 1691735, related citations] [Full Text]

  7. Kajimura, S., Aida, K., Duan, C. Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc. Nat. Acad. Sci. 102: 1240-1245, 2005. [PubMed: 15644436, images, related citations] [Full Text]

  8. Leu, J. I.-J., George, D. L. Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria. Genes Dev. 21: 3095-3109, 2007. [PubMed: 18056423, images, related citations] [Full Text]

  9. Leu, J. I., Crissey, M. A. S., Craig, L. E., Taub, R. Impaired hepatocyte DNA synthetic response posthepatectomy in insulin-like growth factor binding protein 1-deficient mice with defects in C/EBP-beta and mitogen-activated protein kinase/extracellular signal-regulated kinase regulation. Molec. Cell. Biol. 23: 1251-1259, 2003. [PubMed: 12556485, images, related citations] [Full Text]

  10. Leu, J. I., Crissey, M. A. S., Taub, R. Massive hepatic apoptosis associated with TGF-beta-1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice. J. Clin. Invest. 111: 129-139, 2003. [PubMed: 12511596, images, related citations] [Full Text]

  11. Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., Fraenkel, E. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nature Genet. 39: 730-732, 2007. [PubMed: 17529977, images, related citations] [Full Text]

  12. Popovici, R. M., Lu, M., Bhatia, S., Faessen, G. H., Giaccia, A. J., Giudice, L. C. Hypoxia regulates insulin-like growth factor-binding protein 1 in human fetal hepatocytes in primary culture: suggestive molecular mechanisms for in utero fetal growth restriction caused by uteroplacental insufficiency. J. Clin. Endocr. Metab. 86: 2653-2659, 2001. [PubMed: 11397868, related citations] [Full Text]


Patricia A. Hartz - updated : 1/18/2008
Patricia A. Hartz - updated : 8/6/2007
Patricia A. Hartz - updated : 5/5/2006
Patricia A. Hartz - updated : 4/28/2003
Denise L. M. Goh - updated : 4/17/2003
John A. Phillips, III - updated : 8/15/2001
Creation Date:
Victor A. McKusick : 10/7/1988
carol : 08/15/2016
terry : 03/14/2013
mgross : 2/4/2008
terry : 1/18/2008
alopez : 8/6/2007
wwang : 5/10/2006
terry : 5/5/2006
cwells : 5/1/2003
terry : 4/28/2003
carol : 4/17/2003
cwells : 8/22/2001
cwells : 8/15/2001
alopez : 7/21/1998
terry : 5/29/1998
mark : 11/7/1996
mark : 11/7/1996
carol : 5/24/1994
supermim : 3/16/1992
carol : 5/14/1991
supermim : 3/20/1990
supermim : 2/22/1990
supermim : 1/9/1990

* 146730

INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 1; IGFBP1


Alternative titles; symbols

IBP1
PLACENTAL PROTEIN 12
IGF-BP25


HGNC Approved Gene Symbol: IGFBP1

Cytogenetic location: 7p12.3     Genomic coordinates (GRCh38): 7:45,888,488-45,893,660 (from NCBI)


TEXT

Description

Unlike insulin, both IGF I (147440) and IGF II (147470) circulate in plasma tightly bound to specific binding proteins. Two major forms of IGF-binding proteins have been identified in human plasma, a low molecular weight form and a high molecular weight form. The low molecular weight IGF-binding protein (IGFBP1) is synthesized in liver, secretory endometrium, and decidua. It binds both IGF I and IGF II with high affinity.


Cloning and Expression

Brinkman et al. (1988) cloned and sequenced a cDNA encoding a low molecular weight IGF-binding protein from a human placenta cDNA library. Expression of the cDNA encoding what they termed 'IBP-1' in monkey COS cells resulted in the synthesis of a 30-kD protein that binds IGF I and is immunologically indistinguishable from the IGF-binding protein isolated from amniotic fluid or human serum. Northern blotting analysis demonstrated that expression of the IBP1 gene is limited to placental membranes and fetal liver.

Brewer et al. (1988) purified an insulin-like growth factor-binding protein from human amniotic fluid and showed that it potentiates the effects of IGF I in vitro. They used a polyclonal antibody to this protein to isolate a cDNA clone from a human decidua library. They found that the clone encodes a polypeptide of 28,832 Da that includes sequences of 9 tryptic peptides that had been prepared from the purified protein. The protein has 15 cysteines clustered at the amino and carboxy ends of the molecule. Near its C terminus the protein has an RGD sequence (arginine-glycine-aspartic acid) which may account for its ability to attach to cells and to potentiate the biologic actions of IGF I.


Nomenclature

IGFBP1 is also known as amniotic fluid binding protein (AFBP), placental protein-12, alpha-pregnancy-associated endometrial globulin, growth hormone independent-binding protein, binding protein-28, binding protein-26, and binding protein-25 (Ballard et al., 1990).


Gene Structure

Brinkman et al. (1988) found that the IGFBP1 gene has 4 exons and spans 5.9 kb.


Mapping

Brinkman et al. (1988) mapped the IGFBP1 gene to chromosome 7 by Southern analysis of genomic DNA isolated from human-rodent somatic cell hybrids.

Alitalo et al. (1989) localized the IGFBP1 gene to 7p13-p12 by in situ hybridization. Ekstrand et al. (1990) confirmed this assignment by Southern analysis of somatic hybrid cell DNA and by in situ hybridization. Alitalo et al. (1989) described a 2-allele RFLP with allele frequencies that made it useful as a genetic marker for the proximal short arm of chromosome 7.


Gene Function

IGFBP1 is elevated in the fetal circulation of human and animal pregnancies complicated by intrauterine growth retardation (IUGR) caused by placental insufficiency and in utero hypoxia and is believed to restrict fetal growth by sequestering IGFs. Popovici et al. (2001) established highly pure primary cultures of human fetal hepatocytes in vitro and investigated the expression of IGFBP1 and the effects of hypoxia on expression of IGFBP1 mRNA and protein. Hepatocytes were cultured in defined medium, and Northern blot analysis revealed expression of a 1.5-kb IGFBP1 mRNA transcript in hepatocytes cultured under normoxic conditions for 24 hours that did not increase in steady-state levels after 48 hours in culture. Under hypoxic conditions, IGFBP1 mRNA expression increased 3- to 4-fold compared with normoxic controls. Western blot analysis of conditioned medium revealed the presence of IGFBP1, IGFBP2 (146731), IGFBP3 (146732), and IGFBP4 (146733). IGFBP1 was the most abundant IGFBP in conditioned medium, and densitometric analysis revealed a 2.5-fold increase in IGFBP1 under hypoxic, compared with normoxic, conditions, supporting the immunoradiometric assay results. A 3-fold increase in IGFBP3 mRNA, but not other IGFBPs, was noted under hypoxic, compared with normoxic, conditions. The authors concluded that hypoxia upregulates fetal hepatocyte IGFBP1 mRNA steady-state levels and protein, with this being the major IGFBP derived from the fetal hepatocyte. These data also supported a role for the fetal liver as a source of elevated circulating levels of IGFBP1 in fetuses with in utero hypoxia and IUGR.

Using loss- and gain-of-function approaches with zebrafish embryos, Kajimura et al. (2005) demonstrated that Igfbp1 mediated hypoxia-induced embryonic growth retardation and developmental delay. When tested in vitro with cultured zebrafish embryonic cells, Igfbp1 itself had no mitogenic activity, but it inhibited Igf1- and Igf2-stimulated cell proliferation by binding to and inhibiting the activities of IGFs.

In a study comparing the binding of transcriptional regulators to promoter regions across species (human and mouse), Odom et al. (2007) demonstrated that the binding site for HNF6 (604164) in the human IGFBP1 gene is in the promoter region, while that in the mouse Igfbp1 gene is in the first intron.

Liver is generally refractory to apoptosis induced by p53 (TP53; 191170). Leu and George (2007) found that p53 activation led to enhanced expression of IGFBP1 in human hepatoma cells. A portion of intracellular IGFBP1 localized to mitochondria, where it bound the proapoptotic protein BAK (BAK1; 600516). Binding of IGFBP1 to BAK impaired formation of the proapoptotic p53/BAK complex and induction of apoptosis in cultured human and mouse cells and in mouse liver. In contrast, livers of Igfbp1-deficient mice exhibited spontaneous apoptosis accompanied by p53 mitochondrial accumulation and evidence of Bak oligomerization. Leu and George (2007) concluded that IGFBP1 is a negative regulator of the p53/BAK-dependent pathway of apoptosis.


Animal Model

Leu et al. (2003) treated Igfbp1 -/- mice with a normally sublethal dose of Fas agonist. The mice developed massive hepatocyte apoptosis and caspase activation within 3 hours of treatment. Earlier (0.5-1 hour after treatment), Igfbp1-deficient livers had enhanced signaling via the integrin receptor and elevated activated matrix metalloproteinase-9 (MMP9; 120361), a known target of fibronectin signaling and activator of TGF-beta (see TGFB1; 190180). Within 3 hours of treatment, there was elevated expression of active TGFB1, a hepatocyte apoptogen, which correlated with the appearance of the apoptotic process. Igfbp1 -/- mice that were treated with IGFBP1 prior to treatment with Fas agonist were protected against lethality and Fas-mediated apoptotic injury. IGFBP1 treatment suppressed the expression of both MMP9 and TGFB1, supporting their role in the apoptotic process. Igfbp1 -/- mice also displayed increased injury in a toxic hepatic injury model caused by CCl4. Leu et al. (2003) suggested that IGFBP1 may function as a critical survival factor in the liver by suppressing the level and activation of specific proapoptotic factors via its regulation of integrin-mediated signaling.

Experiments with rats indicated that Igfbp1 is one of the most rapidly and highly induced genes in regenerating liver following partial hepatectomy. Leu et al. (2003) found that Igfbp1-null mice developed normally, but liver regeneration after partial hepatectomy was abnormal and was characterized by liver necrosis and reduced and delayed hepatocyte DNA synthesis. The activation of p42 Mapk (176948) and p44 Mapk (601795) and induction of C/EBP-beta (189965) was abnormally reduced following hepatectomy. Cell cycle abnormalities were similar to those observed in hepatectomized C/EBP-beta-null mice in that cyclin A1 (604036) and cyclin B1 (123836) expression was delayed and reduced, whereas cyclin D1 (168461) expression was normal.


REFERENCES

  1. Alitalo, T., Kontula, K., Koistinen, R., Aalto-Setala, K., Julkunen, M., Janne, O. A., Seppala, M., de la Chapelle, A. The gene encoding human low-molecular weight insulin-like growth-factor binding protein (IGF-BP25): regional localization to 7p12-p13 and description of a DNA polymorphism. Hum. Genet. 83: 335-338, 1989. [PubMed: 2478445] [Full Text: https://doi.org/10.1007/BF00291377]

  2. Ballard, F. J., Baxter, R. C., Binoux, M., Clemmons, D. R., Drop, S. L. S., Hall, K., Hintz, R. L., Rechler, M. M., Rutanen, E. M., Schwander, J. C. Report on the nomenclature of the IGF binding proteins. J. Clin. Endocr. Metab. 70: 817-818, 1990.

  3. Brewer, M. T., Stetler, G. L., Squires, C. H., Thompson, R. C., Busby, W. H., Clemmons, D. R. Cloning, characterization, and expression of a human insulin-like growth factor binding protein. Biochem. Biophys. Res. Commun. 152: 1289-1297, 1988. Note: Erratum: Biochem. Biophys. Res. Commun. 155: 1485 only, 1988. [PubMed: 2454104] [Full Text: https://doi.org/10.1016/s0006-291x(88)80425-x]

  4. Brinkman, A., Groffen, C. A. H., Kortleve, D. J., Drop, S. L. S. Organization of the gene encoding the insulin-like growth factor binding protein IBP-1. Biochem. Biophys. Res. Commun. 157: 898-907, 1988. [PubMed: 2849945] [Full Text: https://doi.org/10.1016/s0006-291x(88)80959-8]

  5. Brinkman, A., Groffen, C., Kortleve, D. J., Geurts van Kessel, A., Drop, S. L. S. Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1). EMBO J. 7: 2417-2423, 1988. [PubMed: 2461294] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03087.x]

  6. Ekstrand, J., Ehrenborg, E., Stern, I., Stellan, B., Zech, L., Luthman, H. The gene for insulin-like growth factor binding protein-1 is localized to human chromosomal region 7p14-p12. Genomics 6: 413-418, 1990. [PubMed: 1691735] [Full Text: https://doi.org/10.1016/0888-7543(90)90470-f]

  7. Kajimura, S., Aida, K., Duan, C. Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc. Nat. Acad. Sci. 102: 1240-1245, 2005. [PubMed: 15644436] [Full Text: https://doi.org/10.1073/pnas.0407443102]

  8. Leu, J. I.-J., George, D. L. Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria. Genes Dev. 21: 3095-3109, 2007. [PubMed: 18056423] [Full Text: https://doi.org/10.1101/gad.1567107]

  9. Leu, J. I., Crissey, M. A. S., Craig, L. E., Taub, R. Impaired hepatocyte DNA synthetic response posthepatectomy in insulin-like growth factor binding protein 1-deficient mice with defects in C/EBP-beta and mitogen-activated protein kinase/extracellular signal-regulated kinase regulation. Molec. Cell. Biol. 23: 1251-1259, 2003. [PubMed: 12556485] [Full Text: https://doi.org/10.1128/MCB.23.4.1251-1259.2003]

  10. Leu, J. I., Crissey, M. A. S., Taub, R. Massive hepatic apoptosis associated with TGF-beta-1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice. J. Clin. Invest. 111: 129-139, 2003. [PubMed: 12511596] [Full Text: https://doi.org/10.1172/JCI16712]

  11. Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., Fraenkel, E. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nature Genet. 39: 730-732, 2007. [PubMed: 17529977] [Full Text: https://doi.org/10.1038/ng2047]

  12. Popovici, R. M., Lu, M., Bhatia, S., Faessen, G. H., Giaccia, A. J., Giudice, L. C. Hypoxia regulates insulin-like growth factor-binding protein 1 in human fetal hepatocytes in primary culture: suggestive molecular mechanisms for in utero fetal growth restriction caused by uteroplacental insufficiency. J. Clin. Endocr. Metab. 86: 2653-2659, 2001. [PubMed: 11397868] [Full Text: https://doi.org/10.1210/jcem.86.6.7526]


Contributors:
Patricia A. Hartz - updated : 1/18/2008
Patricia A. Hartz - updated : 8/6/2007
Patricia A. Hartz - updated : 5/5/2006
Patricia A. Hartz - updated : 4/28/2003
Denise L. M. Goh - updated : 4/17/2003
John A. Phillips, III - updated : 8/15/2001

Creation Date:
Victor A. McKusick : 10/7/1988

Edit History:
carol : 08/15/2016
terry : 03/14/2013
mgross : 2/4/2008
terry : 1/18/2008
alopez : 8/6/2007
wwang : 5/10/2006
terry : 5/5/2006
cwells : 5/1/2003
terry : 4/28/2003
carol : 4/17/2003
cwells : 8/22/2001
cwells : 8/15/2001
alopez : 7/21/1998
terry : 5/29/1998
mark : 11/7/1996
mark : 11/7/1996
carol : 5/24/1994
supermim : 3/16/1992
carol : 5/14/1991
supermim : 3/20/1990
supermim : 2/22/1990
supermim : 1/9/1990