Disease relevance of Igfbp2

• Overexpression of insulin-like growth factor-binding protein-2 in C6 glioma cells results in conditional alteration of cellular growth [1].
• One of the mechanisms contributing to increased IGFBP levels in uremia is increased hepatic gene expression of IGFBP-1 and IGFBP-2 [2].
• Seven days after the contusion, IGFBP-2 expression was only moderately up-regulated and again concentrated around the injury [3].
• IGF-binding protein-2 is induced during development of urinary bladder hypertrophy in the diabetic rat [4].
• Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis [5].

Psychiatry related information on Igfbp2

• In conclusion, there exists a critical period during the perinatal development of the rat, when thyroid hormone is essential for a subsequent normal IGFBP-2 ontogenic pattern [6].

High impact information on Igfbp2

• Angiotensin II markedly reduced plasma IGF I levels (56 and 41% decrease at 1 and 2 wk, respectively) and IGF binding protein-3 levels, and increased IGF binding protein-2 levels, a pattern suggestive of dietary restriction [7].
• Serum-deprived SMC-conditioned medium contains IGFBPs of 38 to 45 kD (only in confluent cultures), 30 kD (possibly IGFBP-2), 28 kD, and 24 kD (IGFBP-4), the latter being the most abundant [8].
• Even though microglia were activated in both locations 2-4 d after transfer, astrocytic levels of IGF-I, IGFR-I and IGFBP-2 mRNA and peptide did not differ significantly from those observed in controls [9].
• The sites of IGFBP-2 gene expression were associated with immunoreactive IGF-II at the apical surface of the epithelium [10].
• In situ hybridization studies with late gestation (days 16, 18 and 20) fetal rat lung using a cDNA probe for IGFBP-2 showed strong gene expression in the fetal lung epithelial structures (alveoli and airways) [10].

Biological context of Igfbp2

• Igfbp2 gene expression was transiently upregulated during the contractile phase of gestation (Days 21-23) solely in the gravid horn of unilaterally pregnant rats, but it was not affected in P4- or RU486-treated animals, supporting a role for mechanical stretch imposed by the growing fetuses [11].
• We observed a dramatic up-regulation of insulin-like growth factor binding protein-2 (IGFBP-2) mRNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion [3].
• Given the critical roles played by insulin-like growth factors in cellular mitogenesis, differentiation, and cell death, and that IGFBP-2 is the major brain resident IGFBP, we assessed IGFBP-2 expression in primary cortical neuroncultures subsequent to lithium treatment [12].
• Indeed, we show that the addition of conditioned medium from growth-arrested cells on proliferative cells results in down-regulation of IGFBP-2 and increased expression of IGF-II and type 2 IGF receptor mRNA [13].
• From the results presented in this study, it can be suggested that IGFBP-2, IGF-II, and type 2 IGF receptor play an important role in the transition of lung alveolar epithelial cells in and out of the cell cycle [13].

Anatomical context of Igfbp2

• IGFBP-2 mRNA was localized only in the luminal epithelium of the endometrium [14].
• Both IGFBP-1 and IGFBP-2 mRNAs transiently appeared in the pancreas between postnatal weeks 2 and 3 and declined in the adult [15].
• IGF-II and IGFBP-2 mRNAs were not detected in perinatal uteri [16].
• A significant upregulation of IGFBP-2 mRNA and protein was detected in astrocytes after KCl exposure This upregulation was reduced by MK-801 treatment [17].
• We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons [5].

Associations of Igfbp2 with chemical compounds

• The effects on IGFBP-2 ontogeny, and IGFBP-4 expression in the mature animal, however, are either direct thyroid hormone effects, or mediated by some other route, independent of GH, IGFs, or IGF receptors [18].
• Insulin-like growth factor binding protein-2 expression is decreased by lithium [12].
• Linkage of the C-terminal cysteine residues is identical to that of IGFBP-2, -5 and -6 (C15 to C16, C17 to C18 and C19 to C20) [19].
• Taken together, these findings indicate that upregulation of IGFBP-2 by depolarization is mediated by NMDA receptors, and, as no neuronal damage was detected, astrocytic NMDA receptors may be responsible for this upregulation [17].
• IGFBP-2 mRNA was clustered throughout the anterior pituitary and was significantly higher in the estrogen-treated groups as noted above for [125I]IGF-I binding [20].

Physical interactions of Igfbp2

• We show in this study that insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) accumulates to high levels in culture medium of growth-arrested type 2 cells [13].
• In the CSF, transported IGF-II is complexed to IGFBP-2 and essentially demonstrates an endocrine mode of action with a balance of locally produced IGFBPs modulating its bioactivity in the wound [21].
• To test whether hormonal regulation of IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) may be involved in the accumulation of IGF-I in tanycytes, we assessed the effect of ovarian hormones on the levels of these molecules in the mediobasal hypothalamus of adult female rats [22].
• Insulin-like growth factor binding protein-2 binds to cell surface proteoglycans in the rat brain olfactory bulb [23].
• IGFBP-2 also bound the proteoglycan aggrecan, an effect reduced by digestion of its glycosaminoglycans [23].

Regulatory relationships of Igfbp2

• IGF-I stimulated gene expression of IGFBP-2 and IGFBP-4 [24].
• Immunoblotting showed that following DEX exposure, IGFBP-3 and -6 were up-regulated whereas IGFBP-2, -5, and the 24 kDa band were down-regulated [25].
• Primary cell cultures of 18f lung epithelia express IGFBP-2 while fibroblasts from the same animals express only IGFBP-4 [26].
• IGFBP-2 and -3 in excess inhibited IGFBP-5 heterogeneous nuclear RNA levels, as determined by RT-PCR, and did not alter the half-life of IGFBP-5 mRNA in transcriptionally arrested Ob cells [27].
• IGFBP-2 mRNA levels were stimulated by TGF-beta 1 (2.0 ng/ml) and suppressed by insulin (5.0 micrograms/ml) [28].

Other interactions of Igfbp2

• Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed [29].
• Western antibody analysis identified IGFBP-2 and IGFBP-5 within the 30/32 kDa complex, while gel mobility shift on SDS-PAGE following deglycosylation determined that IGFBP-3 comprised the 38-47 kDa complex [30].
• Depolarization induces insulin-like growth factor binding protein-2 expression in vivo via NMDA receptor stimulation [17].
• In the neural lobe, [125I]IGF-I binding, IGFBP-2 mRNA, IGF-I receptor mRNA, and IGF-I mRNA were all uniformly distributed and did not differ between groups [20].
• In particular, ovariectomy decreased the IGFBP-2 mRNA content in the protein-restricted rats and the IGFBP-6 mRNA content in the rats fed on the control diet [31].

Analytical, diagnostic and therapeutic context of Igfbp2

• Cloning and sequence determination of bovine insulin-like growth factor binding protein-2 (IGFBP-2): comparison of its structural and functional properties with IGFBP-1 [32].
• Total RNA was extracted from fresh day 1, day 6, and cultured OBs for Northern blotting using complementary DNA probes for IGFBP-2, -3, -4, and -5 [33].
• IGFBP-1 and IGFBP-2 Western immunoblot analyses were also performed in serum [34].
• Immunoblotting showed that the changes in the 29,000 to 34,000 Mr forms observed by ligand blotting appeared to be predominantly due to changes in IGFBP-2 [35].
• In all samples showing Western ligand binding profiles corresponding to IGFBP-2, identification was established by immunoprecipitation [36].

References