Disease relevance of IGFBP4

• IGFBP-4 was the predominant IGFBP expressed by both cell types and did not change with exposure to hypoxia [1].

High impact information on IGFBP4

• The PCR-derived probe for IGFBP4 was used to screen a bovine pulmonary artery cDNA library for a full-length bovine IGFBP4 cDNA clone [2].
• Thus, cultured bovine endothelial cells synthesize and secrete IGFBP2, IGFBP3, and IGFBP4 and have mRNA encoding IGFBP2-6 [2].
• IGFBP4 protein was purified from bovine pulmonary artery-conditioned medium, shown to have N-terminal amino acid sequence DEAIHCPPCSEEKLARCR (identical to human IGFBP4) and to be secreted in glycosylated and nonglycosylated forms [2].
• This clone contained an open reading frame encoding a 258-amino acid protein that was 97% identical to human IGFBP4, 268 basepairs of 5'-untranslated region, and a longer 1044 basepairs of 3'-untranslated region [2].
• Differences between F1 and F2-F4 in diameter, estradiol, free IGF-I, and IGFBP-4 and -5 proteolytic activity were even greater in group 3 [3].

Biological context of IGFBP4

• TGF-beta1 expression and induction of apoptosis was facilitated by the suppression of somatotropic pathway during drying off, manifested with down-regulation of GH-R and IGF-IRalpha, and up-regulation of IGFBP-4 and -5 [4].
• Insulin-like growth factor binding protein 4 (IGFBP4) was purified to homogeneity from conditioned media of bovine pulmonary artery endothelial cells and shown to have the N-terminal amino acid sequence DEAIHCPPCS, a sequence unique to IGFBP4 [5].
• Overall, these results suggest that during terminal development of follicles to the preovulatory stage in domestic animal species, the increase in IGF bioavailability might enhance IGFBP-4 degradation [6].
• To examine the hypothesis that proteolysis of IGFBP-4 and -5 plays a critical role in selection of the dominant follicle, we isolated follicles at various stages during the first wave of follicular development during the bovine estrous cycle, using ultrasonography to follow follicular growth [3].
• In conclusion, selection of the dominant follicle is associated with increased granulosa cell aromatase activity followed by increased cAMP response to LH and follicular fluid oestradiol concentrations, and decreased follicular fluid concentrations of IGFBP-4 and -5 within 2 days after ovulation [7].

Anatomical context of IGFBP4

• IGF-1R, IGFBP-4 and IGFBP-5 mRNA expression were not significantly altered by follicle size or health, but IGFBP-5 tended to increase in atretic follicles [8].
• In conclusion follicular dominance was associated with low or decreased follicular fluid concentrations of IGFBP-4 and -5, increased estradiol and differential regulation of IGFBP production [9].
• We conclude that the connective tissue distribution previously reported for IGFBPs in conditioned media of pulmonary artery endothelial cells is due to IGFBP4 [5].
• Both forms of IGFBP4 crossed the capillary boundary of the heart and distributed primarily in subendothelial connective tissue components with a connective tissue/cardiac muscle distribution ratio of 20:1 for the glycosylated fraction and 27:1 for the nonglycosylated fraction [5].
• In Experiment 3B, production of IGFBP-2/-5 by granulosa cells was attenuated in the presence of cortisol with or without insulin and insulin plus glucagon; glucagon and cortisol decreased production of IGFBP-4 by granulosa cells [10].

Associations of IGFBP4 with chemical compounds

• Concentrations of P4 were correlated positively (r > 0.4; P < 0.05) with IGFBP-4 and -5 [11].
• Heparin-binding peptides derived from the C-terminal domain of IGFBP-3 or -5 inhibited IGFBP-4 degradation [6].
• The amount of 28-29-kDa IGFBPs (small form of IGFBP-5 and [or] glycosylated form of IGFBP-4) was inversely associated with concentrations of androstenedione [12].
• Both IGFBP-2 and IGFBP-4 mRNA levels were consistently reduced in stretched cells but remained comparable to those of the control cells when the angiotensin II transducing pathway was blocked by inhibitors prior to the application of mechanical strain [13].
• IGF-I (1 nM) enhanced release of IGFBP-3 while dexamethasone (1 nM) diminished release of IGFBP-4 [14].

Regulatory relationships of IGFBP4

• An excess of IGF-I enhanced IGFBP-4 degradation [6].

Other interactions of IGFBP4

• The expression of three genes (IGF2R, IGFBP-4, and IGF2) in some tissues showed significant differences between AF cell-derived and FF cell-derived clones [15].
• In ligand blots IGFBP-3 and IGFBP-4 appeared as the most prominent species [14].
• Other heparin-binding peptides derived from CTGF, HIP, and vitronectin also inhibited IGFBP-4 degradation, except in porcine follicles [6].
• In contrast, insulin or glucagon alone had no effect on production of the IGFBP-4 by thecal cells but when combined inhibited IGFBP-4 production [10].
• The four largest follicles (F1-F4) were dissected and concentrations of steroids, IGFBPs and free IGF-I and levels of proteolytic activity for IGFBP-4 and -5 in the follicular fluid were determined [3].

Analytical, diagnostic and therapeutic context of IGFBP4

• Western immunoblot analysis confirmed the identity of the 24-kDa, 31-kDa, and 36-kDa species as IGFBP-4, -5, and -2, respectively [16].
• Northern blot analysis reflected increased IGFBP-3 mRNA but not decreased IGFBP-4 mRNA [17].

References