Disease relevance of Hbegf

• The levels of HB-EGF and AR transcripts were significantly elevated in skin tumors (both papillomas and squamous cell carcinomas) induced by initiation-promotion protocols [1].
• Here we investigate the role of HB-EGF in epidermal hyperplasia induced by all-trans retinoic acid (tRA) treatment [2].
• Mutated DT toxin (CRM197) is devoid of toxicity but it neutralizes HB-EGF binding to EGFR [3].
• HB-EGF knockout mice displayed enlarged heart valves, and over half of these mice died during the first postnatal week, while survivors showed cardiac hypertrophy [4].
• Overexpression of heparin-binding EGF-like growth factor in mouse pancreas results in fibrosis and epithelial metaplasia [5].

Psychiatry related information on Hbegf

• Our findings suggest that regional and temporal differences in the availability of endogenous HB-EGF may serve to limit the response of EGL neuroblasts to opioids, and HB-EGF may be neuroprotective in opiate drug abuse [6].

High impact information on Hbegf

• In mice with cardiac hypertrophy, KB-R7785 inhibited the shedding of HB-EGF and attenuated hypertrophic changes [7].
• KB-R7785 bound directly to ADAM12, suggesting that inhibition of ADAM12 blocked the shedding of HB-EGF [7].
• Through this approach the gene encoding heparin-binding epidermal growth factor (HB-EGF) was identified as an immediate-early transcriptional target of oncogenic Raf kinases [8].
• BACKGROUND & AIMS: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is expressed in both normal pancreatic islets and in pancreatic cancers, but its role in pancreatic physiology and disease is not known [5].
• RESULTS: Mice overexpressing HB-EGF in pancreatic islets showed both endocrine and exocrine pancreatic defects [5].

Chemical compound and disease context of Hbegf

• At 4 h following pilocarpine-induced seizures, expression of NGF, BDNF, HB-EGF, and FGF-2 increased only in the mice manifesting tonic-clonic convulsions and not in mice without seizures [9].

Biological context of Hbegf

• Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors [10].
• Our results provide the first evidence that HB-EGF is a crucial regulator of epithelial morphogenesis during organ development, highlighting the importance of its processing by metalloproteinases [11].
• Chlorate treatment did not significantly alter the ability of HB-EGF to compete with 125I-EGF for cell surface binding sites, however, heparin and hexadimethrine reduced the ability of HB-EGF to compete for 125I-EGF binding [12].
• In conclusion, these findings suggest that the mechanism of ET-1-induced vasoconstriction involves HB-EGF-mediated transactivation of the EGFR [3].
• Consistent with the phenotype, HB-EGF transcripts were localized to endocardial cells lining the margins of wild-type valves [13].

Anatomical context of Hbegf

• Thus, induction of keratinocyte migration is conveyed through EGFR, promoted by endogenous HB-EGF and requires GSK-3alpha activity [14].
• HB-EGF mRNA was detected in developing SMG by RT-PCR analysis and was expressed mainly in epithelium and weakly in mesenchyme of the embryonic SMG [11].
• An in vitro assay using an EGF receptor ligand-dependent cell line, EP170.7 cells, allowed us to detect the growth factor activity in SMG-conditioned media, which was significantly reduced by anti-HB-EGF antibody [11].
• Involvement of heparin-binding EGF-like growth factor and its processing by metalloproteinases in early epithelial morphogenesis of the submandibular gland [11].
• Multiple trophic actions of heparin-binding epidermal growth factor (HB-EGF) in the central nervous system [15].

Associations of Hbegf with chemical compounds

• Together, our observations suggest that retinoid receptor heterodimers located in differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in turn stimulates basal cell growth via intercellular signaling [10].
• It was concluded that HB-EGF activation of receptor tyrosine kinases is essential for normal heart function [16].
• Epithelial morphogenesis was inhibited by a synthetic peptide corresponding to the heparin-binding domain of HB-EGF and by anti-HB-EGF neutralizing antibody [11].
• Unexpectedly, however, neither chlorate nor hexadimethrine treatment caused an inhibition of HB-EGF-induced mitogenic activity [12].
• A single topical treatment of either 12-O-tetradecanoylphorbol-13-acetate (TPA) or chrysarobin or a single full-thickness wound induced the expression of HB-EGF and AR in mRNA samples isolated from whole mouse skin [1].

Enzymatic interactions of Hbegf

• It was concluded that MMP-3 cleaves HB-EGF at a specific site in the JM domain and that this enzyme might regulate the conversion of HB-EGF from being a juxtacrine to a paracrine/autocrine growth factor [17].

Regulatory relationships of Hbegf

• The effect of HB-EGF was also blocked by the EGF receptor (EGFR/ErbB1) inhibitors PD153035 and PD158780, implicating EGFR in HB-EGF-induced cell proliferation [18].
• Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to deltaRaf-1:ER [19].
• Taken together, it was concluded that during skeletal muscle cell differentiation, MyoD plays a direct role in activating HB-EGF gene expression and that HB-EGF protein is expressed preferentially in myotubes and in its membrane-anchored form [20].
• We conclude that HB-EGF stimulates neurogenesis in proliferative zones of the adult brain that are also affected in ischemia and that it does so by interacting with EGFR/ErbB1 and possibly NRDc [21].
• This investigation demonstrates that the HB-EGF gene is expressed in the mouse uterine luminal epithelium surrounding the blastocyst 6-7 hours before the attachment reaction that occurs at 2200-2300 hours on day 4 of pregnancy [22].

Other interactions of Hbegf

• We find that, like TGFalpha, HB-EGF stimulates the proliferation of CNS astrocytes and multipotent progenitors [15].
• These results indicate that expression of HB-EGF and generation of its soluble form, followed by activation of EGFR and ErbB2, are pivotal processes in tRA-induced epidermal hyperplasia [2].
• The neurotrophic actions of HB-EGF and TGFalpha are accompanied by an elevation in immunoreactive dual phosphorylated mitogen-activated protein kinase (MAP kinase) in neurons, providing evidence that the MAP kinase cascade mediates these actions [15].
• Soluble form of heparin-binding EGF-like growth factor contributes to retinoic acid-induced epidermal hyperplasia [2].
• These results suggest that cardiac valvulogenesis is dependent on EGFR activation by TACE-derived soluble HB-EGF, and that EGFR signaling is required to regulate bone morphogenetic protein signaling in this context [13].

Analytical, diagnostic and therapeutic context of Hbegf

• In situ hybridization studies demonstrate that HB-EGF mRNA is present within the brainstem as early as E14 and subsequently is found in the developing cortical plate, hippocampus, cerebellar Purkinje cells and ventrobasal thalamus, among other brain areas [15].
• To determine whether the activity produced by mIL5 cells is attributed to FGF-2 or HB-EGF, three approaches were used: heparin-affinity chromatography, Western blotting, and immunoneutralization [23].
• MVD was also examined in human colorectal tumor and resection margin normals and correlated with serum-amidated gastrin levels (via RIA) and HB-EGF protein expression (via immunohistochemistry) [24].
• In addition, immunostaining and laser confocal microscopy detected HB-EGF protein in C2C12 myotubes but not in myoblasts [20].
• Northern blotting experiments using the HB-EGF clones as probes revealed HB-EGF transcript expression in multiple tissues, particularly lung, skeletal muscle, brain, and heart [25].

References