Disease relevance of Igfbp6

• In contrast, the treatment of pregnant rats with the P4 receptor antagonist RU486 on Day 19 induced preterm labor and the premature decrease of Igfbp6 gene expression [1].

High impact information on Igfbp6

• Human IGFBP-6 possesses a single Asn-linked glycosylation site near the carboxyl-terminal, whereas no potential Asn-linked glycosylation sites are present in the rat sequence [2].
• A single 1.3-kilobase IGFBP-6 mRNA was detected by Northern analysis in all rat tissues examined, including testis, intestine, adrenal, kidney, stomach, spleen, heart, lung, brain, and liver, indicating that this BP is a ubiquitous protein [2].
• Using amino acid sequence information from a tryptic fragment of pig IGFBP-6 to prepare a probe, cDNA clones encoding rat and human IGFBP-6 have been isolated and characterized [2].
• Finally, and most strikingly, IGFBP-6 expression, barely detectable in the d7.0 myometrium, gradually increases until it is very strongly transcribed during the placental stages [3].
• CONCLUSIONS: In the diabetic (mRen-2)27 rat, IGFBP-6 is downregulated and IGFBP-5 is upregulated by induction of diabetes [4].

Biological context of Igfbp6

• Igfbp6 gene expression profile paralleled plasma progesterone (P4) concentrations, peaking during the synthetic phase (Days 17-19) and decreasing thereafter [1].
• The rat IGFBP-6 gene spans 5.1 kb of the genomic sequence and contains four exons interrupted by three introns of approximately 2.4, 0.2 and 1.2 kb in length, respectively [5].
• We now isolated the IGFBP-6 gene from a rat genomic library and determined its organization as well as the DNA sequence at the 5' flanking region of the gene [5].
• The promoter region of the rat IGFBP-6 gene is devoid of a TATA or a CAAT consensus sequence motif, but putative regulatory cis elements, including a Sp1, an estrogen receptor binding site and a retinoic acid responsive element, are present in the promoter region [5].
• The robust upregulation of IGFBP-6 mRNA in lesioned motoneurons suggests that this binding protein may be of special relevance for the severed cells [6].

Anatomical context of Igfbp6

• Taken together, the data show that IGFBP-6 is a new negative effector of oligodendrocyte survival and differentiation [7].
• In addition, IGFBP-6 reduced the IGF-stimulated expression of two myelin proteins, CNPase and MAG [7].
• We demonstrate that IGF-binding protein 6 (IGFBP-6) is expressed and localized to the Golgi complex in rat oligodendrocyte precursor (O2A) cells [7].
• We conclude that chimeras of IGFBP-6 and IGFBP-3(6) clearly differ from IGFBP-4(3) in their ability to bind specifically to endothelial cells and in their capacity to undergo transendothelial transportation in the perfused heart [8].
• IGFBP-6 mRNA, the least abundant, was expressed mainly in fibroblasts associated with renal blood vessels and the ureter [9].

Associations of Igfbp6 with chemical compounds

• Administration of P4 at late pregnancy (starting from Day 20) to maintain elevated plasma P4 concentrations blocked the onset of labor and prevented the fall in Igfbp6 mRNA levels [1].
• IGFBP-6 mRNA expression could be reduced by addition of basic fibroblast growth factor and progesterone while estrogen increased IGFBP-6 mRNA [7].
• In conclusion, cortisol stimulates IGFBP-6 expression in Ob cells by transcriptional mechanisms [10].
• Cycloheximide at 3.6 microM decreased IGFBP-6 transcripts and prevented the stimulatory effect of cortisol [10].
• The effect of dexamethasone on IGFBP-6 levels was therefore studied [11].

Physical interactions of Igfbp6

• IGFBP-6 binds IGF II with high affinity and prevents IGF II-mediated effects [12].

Regulatory relationships of Igfbp6

• In conclusion, TGF beta 1 inhibits IGFBP-6 expression in Ob cells by transcriptional mechanisms [13].

Other interactions of Igfbp6

• We found no evidence for expression of either IGFBP-1 or IGFBP-6 [14].
• In diabetic rats, reduced levels of IGFBP-6 mRNA were detectable, whereas levels of IGFBP-5 mRNA were increased in the inner and outer retina, rods and cones, iris, cornea, and ciliary body [4].
• Messenger RNAs for IGFBP-3 to IGFBP-6 localized to choroidal endothelial cells and chromatophores and also to the inner pigmented epithelium of the ciliary processes [15].
• IGFBP-6 mRNA levels remained unchanged, IGFBP-2 levels decreased and IGFBP-4 and -5 increased over 1, 5, and 9 days after serum reduction [16].
• Denervation resulted in dramatic up-regulation of IGFBP-4 and -5 transcripts but there was no change in IGFBP-6 [16].

Analytical, diagnostic and therapeutic context of Igfbp6

• 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 [17].
• Isolation and molecular cloning of insulin-like growth factor-binding protein-6 [2].
• Retinoic acid caused a time- and dose-dependent increase in IGFBP-6 mRNA levels, as determined by Northern blot analysis [12].
• Treatment with cortisol also increased IGFBP-6 polypeptide levels in the medium, as determined by Western immunoblot analysis [10].

References