Disease relevance of Igfbp4

• Insulin-like growth factor binding protein-4 gene expression is induced by transfection of gap junction connexin43 gene in a C6 glioma cell line [1].
• 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 [2].
• Hypertension increases insulin-like growth factor binding protein-4 mRNA levels in rat aorta [3].
• By RIA, plasma IGFBP-1 levels in uremia were increased 4-fold; by Western immunoblot, plasma IGFBP-2 levels were increased 7-fold and plasma IGFBP-4 levels were increased 2-fold compared with both control groups [4].
• 5. These results suggest that the insulin deficiency and chronic hyperinsulinemia in diabetes upregulate the IGF-1 receptor and downregulate IGFBP-4 and IGFBP-5 in the aorta [5].

High impact information on Igfbp4

• Northern hybridization showed a 2-3-fold increase in IGFBP-4 and IGFBP-5 messenger RNA from inflamed colon [6].
• In summary, SMCs elaborate a cation-dependent protease in a confluence-dependent fashion, which degrades bound IGFBP-4 and likely releases free structurally intact IGF-I, presumably to interact with the cell surface receptor and/or other IGFBPs [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 [7].
• IGF-I and IGF-II but not insulin evoked a marked decrease of IGFBP-4 as early as 4 hours after treatment [7].
• Expression and insulin-like growth factor-dependent proteolysis of insulin-like growth factor-binding protein-4 are regulated by cell confluence in vascular smooth muscle cells [7].

Chemical compound and disease context of Igfbp4

• Intraperitoneal triiodothyronine (T3) administration to hypothyroid rats resulted in renal hypertrophy associated with a significant upregulation of IGFBP-4 expression with increased levels of renal IGFBP-4 mRNA and serum protein [8].

Biological context of Igfbp4

• This indicates that glycosylation of IGFBP-4 does not affect its binding to IGF-I [9].
• A plasmid was constructed to express rat IGFBP-4 as a thioredoxin fusion protein that included a hexahistidine sequence to permit affinity purification [9].
• IGFBP-4 mRNA was confined to interstitial mesenchyme and its abundance peaked at days 16 to 19 of gestation [10].
• In conclusion, loading of tendon tissue results in an upregulation of IGF-I, IGFBP-4, and procollagen and is associated with an increase in tendon mass [11].
• These data are consistent with the predicted changes for IGFBPs on O2 exposure except that the generally growth-inhibitory IGFBP-4 was increased at sites of active cell proliferation [12].

Anatomical context of Igfbp4

• IGFBP-2 mRNA was expressed in glomeruli, medullary ray collecting ducts, pelvic smooth muscle and uroepithelium, and the papilla tip; IGFBP-3 mRNA was localized to the cortical interstitium, whereas IGFBP-4 mRNA was expressed in proximal tubules, medullary ray collecting ducts, and glomeruli [13].
• In the decidual vasculature at Day (d) 8.0, both IGFBP-3 and IGFBP-4 mRNAs are detected in dilating blood vessels, with BP-3 most prominent in the antimesometrial plexus and BP-4 primarily at the mesometrial pole [14].
• Activation of protein kinase-A (PKA) in rat granulosa cells has been shown to modulate the relative expression of IGFBP-4 and -5 transcripts and proteins [15].
• IGFBP-4 mRNA was localized only in the luminal epithelium of the endometrium [16].
• IGFBP-3 and IGFBP-4 mRNAs were detected in both the liver and pancreas throughout the developmental period studied [17].

Associations of Igfbp4 with chemical compounds

• The fusion protein was expressed in E.coli, purified using nickel-chelate affinity chromatography and cleaved by tobacco etch virus (TEV) protease to produce mature rat IGFBP-4 with an additional glycine residue at the N-terminus [9].
• IGFBP-1 to -3 and -5 each contain 18 conserved cysteine residues, IGFBP-6 lacks two of the twelve N-terminal cysteines, while IGFBP-4 has two additional cysteines in the central region [9].
• AtRA and thyroid hormone act synergistically in increasing hepatic IGFBP-4 expression [18].
• IGFBP-4 levels were lower at day 14 in Dex-treated cultures than in controls but higher at day 20 [19].
• Retinoic acid increases insulin-like growth factor-binding protein-4 expression in cultured rat hepatocytes [18].

Regulatory relationships of Igfbp4

• Interestingly, IGFBP-4 mRNA was markedly induced in confluent relative to sparsely grown SMCs in an IGF-I independent fashion [7].
• IGFBP-3 messenger RNA (mRNA) levels were decreased to 50% of control levels but IGFBP-4 mRNA levels were paradoxically increased in the hypothyroid animals [20].
• Primary cell cultures of 18f lung epithelia express IGFBP-2 while fibroblasts from the same animals express only IGFBP-4 [21].
• The ability of TGF-alpha to regulate insulin-like growth factor binding protein-4 (IGFBP-4), was investigated [22].

Other interactions of Igfbp4

• The binding affinities of the recombinant protein and IGFBP-4 secreted by rat cells to IGF-I were compared using a newly developed binding assay [9].
• However IGFBP-4 seems to be the only IGFBP with no potential to enhance the mitogenic actions of the IGFs [9].
• IGFBP-3 mRNA increased in amount immediately following birth, while the quantity of IGFBP-4 mRNA increased sharply in liver from postnatal day 21, but declined in the pancreas. mRNA for IGFBP-5 or -6 was undetectable in either tissue [17].
• IGFBP-4 immunoreactivity was restricted to the apex of the olfactory epithelium [23].
• As opposed to the actions of other growth factors, TGF-beta 1 substantially lowered the levels of IGFBP-2 and IGFBP-4 [24].

Analytical, diagnostic and therapeutic context of Igfbp4

• The protease does not affect the structure of IGF-I as determined by reverse-phase high-performance liquid chromatography and size-exclusion chromatography of 125I-IGF-I incubated for up to 24 hours with SMC-conditioned medium containing IGFBP-4 [7].
• In contrast, IGFBP-3 and IGFBP-4 mRNAs tended to decrease with ovariectomy and increase with hormone repletion [25].
• IGFBP-4 mRNA abundance was measured by Northern blot and protein production was evaluated by Ligand blot on hepatocyte-conditioned culture media [18].
• The levels of IGFBP-2, IGFBP-3, and IGFBP-4 mRNAs were likewise unchanged following nephrectomy [26].
• By immunoprecipitation and ligand blotting, we have proved that the 24 kilodalton protein, which appeared at 25 kilodalton in the present study, is IGFBP-4, whose level was strongly enhanced by basic fibroblast growth factor (bFGF) and platelet-derived growth factor BB homodimer [24].

References