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Gene Review

Igfbp5  -  insulin-like growth factor binding protein 5

Rattus norvegicus

Synonyms: IBP-5, IGF-binding protein 5, IGFBP-5, Igfbp-5, Insulin-like growth factor-binding protein 5
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Disease relevance of Igfbp5


High impact information on Igfbp5

  • The effects of IGFs are significantly modulated by IGFBPs secreted by myoblasts in serum-free medium, inhibitory IG-FBPs-4 and -6 are expressed and secreted by L6A1 myoblasts, while expression of IGFBP-5 rises dramatically as differentiation proceeds [6].
  • Northern hybridization showed a 2-3-fold increase in IGFBP-4 and IGFBP-5 messenger RNA from inflamed colon [2].
  • Finally, although these residues lie within a major heparin-binding site in IGFBP-5 and -3, we also show that the mutations in C-Term have no effect on heparin binding [7].
  • Incubation of osteoblasts with the mRNA transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole demonstrated that PGE2 enhanced IGFBP-5 mRNA stability by 2-fold, increasing the t1/2 from 9 to 18 h [8].
  • In this study, we show that transcriptional and post-transcriptional events initiated by PGE2 collaborate to enhance IGFBP-5 gene expression in primary fetal rat osteoblast cultures [8].

Chemical compound and disease context of Igfbp5


Biological context of Igfbp5


Anatomical context of Igfbp5

  • These data suggest that IGF-I modulates its activity in cultured rat growth plate chondrocytes by the synthesis of both inhibitory (IGFBP-3) and stimulatory (IGFBP-5) binding proteins [11].
  • This technique showed that IGFBP-3 mRNA transcripts were observed mainly in endothelial cells of tumor vasculature, although they were also detected in stromal cells, IGFBP-4 was present mainly in tumor stroma cells, and IGFBP-5 mRNA was expressed predominantly in the epithelial cells of this tumor [1].
  • Comparable results regarding IGFBP-5 were obtained in the mesenchymal chondrogenic cell line RCJ3.1C5.18, which does not express IGFBP-3 [11].
  • Tumors arising from injection of long term cultured cells that were injected into isologous rats contained high amounts of mRNA transcripts for IGFBP-5, suggesting the presence, in vivo, of positive regulators for the expression of this BP [1].
  • Tumor cells cultured in the presence of insulin displayed a 2.2- to 2.5-fold increase in the expression of IGFBP-5 [1].

Associations of Igfbp5 with chemical compounds


Physical interactions of Igfbp5

  • Insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) is an autocrine and paracrine factor that modulates the effects of IGFs [15].
  • Previous findings have described the reduction in affinity of IGFBP-5 for IGFs that occurs after complexation of the binding protein with heparin or other components of the extracellular matrix (ECM) and have postulated that such an interaction may result in conformational changes in protein structure, affecting subsequent IGF interaction [16].

Regulatory relationships of Igfbp5


Other interactions of Igfbp5

  • In conclusion, IGF-I and RA modify the synthesis and secretion of IGFBP-5 in rat Ob cells through pathways that may involve increased transcription and elongation and/or altered processing of heterogenous nuclear RNA [13].
  • CONCLUSION: The dramatic changes in the expression of IGF-I, IGF-II and IGFBP-5 throughout postnatal development suggest that these factors play important roles in the development of this gland and that their actions are highly interrelated [21].
  • IGFBP-5 from rat Ob cells appeared as a single band of 31 kilodaltons in both the conditioned medium and the extracellular matrix as determined by Western immunoblots [13].
  • Aging from adult (18 mo) to old animals (30 mo) was associated with decreases in IGFBP-3 mRNA and protein and IGFBP-5 protein only in the soleus muscle [22].
  • Elevated levels of immunoreactive IGFBP-4 in CRF serum are inversely correlated with the standardized heights of these children, whereas levels of IGFBP-5, which circulates mainly as proteolyzed fragments, are positively correlated with growth parameters [23].

Analytical, diagnostic and therapeutic context of Igfbp5


  1. Insulin-like growth factor-binding proteins in R3230AC mammary tumors of intact and diabetic rats. Korc-Grodzicki, B., Ren, N., Hilf, R. Endocrinology (1993) [Pubmed]
  2. Up-regulation of insulinlike growth factor I binding sites in experimental colitis in rats. Zeeh, J.M., Hoffmann, P., Sottili, M., Eysselein, V.E., McRoberts, J.A. Gastroenterology (1995) [Pubmed]
  3. Insulin-like growth factor-I receptor and binding proteins in rat kidney after nephron loss. Hise, M.K., Lahn, J.S., Shao, Z.M., Mantzouris, N.M., Fontana, J.A. J. Am. Soc. Nephrol. (1993) [Pubmed]
  4. Regulation of insulin-like growth factor binding protein-5 messenger ribonucleic acid expression and protein availability in rat osteoblast-like cells. Conover, C.A., Bale, L.K., Clarkson, J.T., Tørring, O. Endocrinology (1993) [Pubmed]
  5. Overexpression of insulin-like growth factor binding protein-5 decreases osteoblastic function in vitro. Durant, D., Pereira, R.M., Canalis, E. Bone (2004) [Pubmed]
  6. Growth hormone and the insulin-like growth factor system in myogenesis. Florini, J.R., Ewton, D.Z., Coolican, S.A. Endocr. Rev. (1996) [Pubmed]
  7. Specific amino acid substitutions determine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I. Shand, J.H., Beattie, J., Song, H., Phillips, K., Kelly, S.M., Flint, D.J., Allan, G.J. J. Biol. Chem. (2003) [Pubmed]
  8. Promoter-dependent and -independent activation of insulin-like growth factor binding protein-5 gene expression by prostaglandin E2 in primary rat osteoblasts. McCarthy, T.L., Casinghino, S., Mittanck, D.W., Ji, C.H., Centrella, M., Rotwein, P. J. Biol. Chem. (1996) [Pubmed]
  9. Differential mRNA expression of insulin-like growth factor system during renal injury and hypertrophy. Hise, M.K., Li, L., Mantzouris, N., Rohan, R.M. Am. J. Physiol. (1995) [Pubmed]
  10. Insulin-like Growth Factors and Their Binding Proteins Define Specific Phases of Myometrial Differentiation During Pregnancy in the Rat. Shynlova, O., Tsui, P., Dorogin, A., Langille, B.L., Lye, S.J. Biol. Reprod. (2007) [Pubmed]
  11. Insulin-like growth factor (IGF)-I stimulates cell proliferation and induces IGF binding protein (IGFBP)-3 and IGFBP-5 gene expression in cultured growth plate chondrocytes via distinct signaling pathways. Kiepe, D., Ciarmatori, S., Hoeflich, A., Wolf, E., Tönshoff, B. Endocrinology (2005) [Pubmed]
  12. Insulin-like growth factor binding protein 5 and type-1 insulin-like growth factor receptor are differentially regulated during apoptosis in cerebellar granule cells. Roschier, M., Kuusisto, E., Suuronen, T., Korhonen, P., Kyrylenko, S., Salminen, A. J. Neurochem. (2001) [Pubmed]
  13. Insulin-like growth factor (IGF) I and retinoic acid induce the synthesis of IGF-binding protein 5 in rat osteoblastic cells. Dong, Y., Canalis, E. Endocrinology (1995) [Pubmed]
  14. Localization of mRNAs for insulin-like growth factor binding proteins 1 to 6 in rat kidney. Price, G.J., Berka, J.L., Edmondson, S.R., Werther, G.A., Bach, L.A. Kidney Int. (1995) [Pubmed]
  15. Transcriptional regulation of insulin-like growth factor-binding protein-5 by prostaglandin E2 in osteoblast cells. Pash, J.M., Canalis, E. Endocrinology (1996) [Pubmed]
  16. Overlap of IGF- and heparin-binding sites in rat IGF-binding protein-5. Song, H., Beattie, J., Campbell, I.W., Allan, G.J. J. Mol. Endocrinol. (2000) [Pubmed]
  17. Distinct sites of insulin-like growth factor (IGF)-II expression and localization in lesioned rat brain: possible roles of IGF binding proteins (IGFBPs) in the mediation of IGF-II activity. Walter, H.J., Berry, M., Hill, D.J., Cwyfan-Hughes, S., Holly, J.M., Logan, A. Endocrinology (1999) [Pubmed]
  18. Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats. Park, I.S., Kiyomoto, H., Alvarez, F., Xu, Y.C., Abboud, H.E., Abboud, S.L. Am. J. Kidney Dis. (1998) [Pubmed]
  19. Interleukin-6 and its soluble receptor regulate the expression of insulin-like growth factor binding protein-5 in osteoblast cultures. Franchimont, N., Durant, D., Canalis, E. Endocrinology (1997) [Pubmed]
  20. Expression of the IGF system in normal and diabetic transgenic (mRen-2)27 rat eye. Bergman, P.B., Moravski, C.J., Edmondson, S.R., Russo, V.C., Bach, L.A., Wilkinson-Berka, J.L., Werther, G.A. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  21. Inverse correlation between insulin-like growth factor (IGF)-binding protein-5 and IGF-I and II during postnatal development of the anterior pituitary gland. González-Parra, S., Rosato, R.R., Chowen, J.A., Argente, J., Groffen, C., Dits, N., Drop, S.L. Horm. Res. (2002) [Pubmed]
  22. Skeletal muscle IGF-binding protein-3 and -5 expressions are age, muscle, and load dependent. Spangenburg, E.E., Abraha, T., Childs, T.E., Pattison, J.S., Booth, F.W. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  23. Intact IGF-binding protein-4 and -5 and their respective fragments isolated from chronic renal failure serum differentially modulate IGF-I actions in cultured growth plate chondrocytes. Kiepe, D., Andress, D.L., Mohan, S., Ständker, L., Ulinski, T., Himmele, R., Mehls, O., Tönshoff, B. J. Am. Soc. Nephrol. (2001) [Pubmed]
  24. Differential expression of IGF system components in proliferating vs. differentiating growth plate chondrocytes: the functional role of IGFBP-5. Kiepe, D., Ciarmatori, S., Haarmann, A., Tönshoff, B. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  25. Suppression of uterine insulin-like growth factor binding protein 5 by estrogen is mediated in part by insulin-like growth factor I. Huynh, H. Int. J. Oncol. (1998) [Pubmed]
  26. Immunohistochemical localization of insulin-like growth factor binding protein-5 in the developing rat nervous system. Cheng, H.L., Sullivan, K.A., Feldman, E.L. Brain Res. Dev. Brain Res. (1996) [Pubmed]
  27. Expression of the genes encoding the rat renal insulin-like growth factor-I system. Rabkin, R., Brody, M., Lu, L.H., Chan, C., Shaheen, A.M., Gillett, N. J. Am. Soc. Nephrol. (1995) [Pubmed]
  28. Differential regulation of IGF-binding protein gene expression by cAMP in rat C6 glioma cells. Wang, L., Ma, X., Yeh, L.C., Adamo, M.L. Endocrinology (2001) [Pubmed]
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