Disease relevance of DTR

• We also show that intracerebral injection of recombinant human HB-EGF protected the nigrostriatal dopaminergic system in an in vivo adult rat model of Parkinson's disease [1].
• Taken together, HB-EGF can also act as an inducer of LOX-1 expression and play an integral role in foam cell transformation, cellular dysfunction, and proliferation of smooth muscle cells in atherogenesis [2].
• CONCLUSIONS: The results obtained suggest that HB-EGF plays a role in stimulating the proliferation of leiomyoma cells and myometrial cells and in inhibiting apoptosis of those cells through augmentation of HER1 expression [3].

High impact information on DTR

• A similar inhibition of migration occurred when BASMC were treated with a synthetic peptide (P21) corresponding to the sequence of the putative heparin-binding domain of HB-EGF [4].
• Heparitinase or chlorate treatment of BASMC diminished the ability of HB-EGF to stimulate BASMC migration by 60-80% [4].
• HB-EGFTM-II was bioactive and stimulated the proliferation of BALB/c 3T3 cells and smooth muscle cells and the motility of smooth muscle cells, albeit with approximately 10-25% of the specific activity of secreted HB-EGF isoforms [5].
• Heparin-binding epidermal growth factor-like growth factor (HB-EGF), whose cDNA has a predicted 208-codon open reading frame, is synthesized as a membrane-spanning precursor that is processed to release mature mitogenic proteins of approximately 73-87 amino acids in length [5].
• Here we report the identification of bovine heparin-binding EGF-like growth factor (HB-EGF) in chromaffin granules and the cloning of the respective cDNA from bovine-derived adrenal gland [1].

Chemical compound and disease context of DTR

• BACKGROUND: The objective of this study was to investigate the comparative effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on the growth of cultured human leiomyoma cells and myometrial cells [3].

Biological context of DTR

• HB-EGF induced phosphorylation of ERK, p38 MAPK and Akt, which were suppressed by ZD1839 [2].

Anatomical context of DTR

• Furthermore, the neurotrophic action of the chromaffin granule extract could be abolished by antiserum to recombinant human HB-EGF [1].
• HB-EGF mRNA and protein was shown in the endoderm, and the protein also was detected immunohistochemically in about 45% of the blastocysts [6].

Associations of DTR with chemical compounds

• METHODS: Isolated cells were subcultured in Phenol Red-free Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 120 h and then stepped down to serum-free conditions for an additional 24 and 48 h in the presence or absence of graded concentrations of HB-EGF (0.1, 1, 10 and 100 ng/ml) [3].

Regulatory relationships of DTR

• Phosphatidylinositol 3-kinase (PI3K) inhibitors also blocked HB-EGF-induced LOX-1 expression [2].

Analytical, diagnostic and therapeutic context of DTR

• HB-EGFTM-II cross-reacted on a Western blot with an antibody directed against the 16 C-terminal amino acids of the cytoplasmic tail of HB-EGF, indicating that it contains a putative transmembrane domain [5].
• Two isoforms of transmembrane HB-EGF (HB-EGFTM) were purified from membrane fractions of infected insect cells by a combination of heparin affinity chromatography and reversed-phase high performance liquid chromatography [5].

References