Disease relevance of Igfbp5

• These findings imply a role for insulin as a regulator of the expression of IGFBP-5 in the R3230AC adenocarcinoma [1].
• CONCLUSIONS: Experimental colitis in rats causes an increase in IGF-I binding to the muscularis propria, which represents increased levels of IGFBP-4 and IGFBP-5 [2].
• These studies suggest that cytosolic hypertrophy of proximal nephron structures is accompanied by membrane hypertrophy with a fixed density of IGF-I receptor and IGF-binding protein-5 [3].
• Another rat osteosarcoma cell line (ROS 17/2.8) did not express IGFBP-5 mRNA and did not secrete 29K IGFBP [4].
• The effects of IGFBP-5 on bone cell growth and osteoblastic function are controversial, and transgenic mice overexpressing IGFBP-5 exhibit osteopenia [5].

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

• During regeneration following folic acid-induced acute renal failure, IGF-I, IGFBP-3, and IGFBP-5 mRNAs declined in abundance approximately two- to threefold [9].

Biological context of Igfbp5

• Igfbp5 gene was induced during postpartum involution [10].
• The IGF-I-induced IGFBP-5 gene expression required de novo mRNA transcription and de novo protein synthesis [11].
• Insulin-like growth factor binding protein 5 and type-1 insulin-like growth factor receptor are differentially regulated during apoptosis in cerebellar granule cells [12].
• IGF-I and RA did not change IGFBP-5 mRNA stability in Ob cells after transcription arrest with the RNA polymerase II inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole [13].
• We describe a prominent downregulation of IGFBP-5 mRNA and protein expression [12].

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

• Insulin-like growth factor (IGF) I and retinoic acid induce the synthesis of IGF-binding protein 5 in rat osteoblastic cells [13].
• Treatment of Ob cells with either IGF-I or all-trans-retinoic acid (RA) caused a time- and dose-dependent increase in IGFBP-5 messenger RNA (mRNA) levels, as determined by Northern blot analysis [13].
• We also show that IGF-I increases IGFBP-5 expression in CGCs and that the downregulation of IGFBP-5 mRNA can be suppressed by inhibiting mRNA synthesis with actinomycin D [12].
• PGE2 treatment stimulated up to a 7-fold rise in steady-state levels of IGFBP-5 mRNA throughout 32 h of incubation [8].
• IGFBP-5 mRNA, the most abundant and widely distributed of the IGFBP mRNAs in the kidney, occurred in the glomerular mesangium and the medullary interstitium as well as in the epithelial cells of the distal nephron [14].

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

• It seems that the expression of IGFBP-5 and IGF1R is regulated to maximize the availability of IGF and the activity of IGF-triggered survival signalling [12].
• Later in the wounding response, levels of IGF-II decline in the CSF and the wound neuropil, possibly with the aid of increased IGFBP-5 levels that may help to locally sequester and down-regulate IGF-II activity [17].
• In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5 [18].
• Interleukin-6 and its soluble receptor regulate the expression of insulin-like growth factor binding protein-5 in osteoblast cultures [19].
• CONCLUSIONS: In the diabetic (mRen-2)27 rat, IGFBP-6 is downregulated and IGFBP-5 is upregulated by induction of diabetes [20].

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

• IGFBP-5 expression was markedly upregulated during the process of differentiation in both cell culture models [24].
• Following ovariectomy, IGFBP-5 is confined in the luminal epithelial layer and longidinal smooth muscle cells [25].
• In the current study, cellular and tissue-specific distribution of IGFBP-5 protein was examined in the developing rodent nervous system using immunohistochemistry [26].
• Because of the physiologic importance of IGF-I and its potential therapeutic properties, the renal sites of mRNA synthesis for IGF-I, IGF-IR, and IGFBP-I through IGFBP-5 were characterized in rat kidney by in situ hybridization [27].
• Site-directed mutagenesis of the region from -14 to -5 led to a loss of the ability of the IGF-binding protein-5 promoter to respond to cAMP [28].

References