Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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heparin binding EGF like growth factor(HBEGF) heparin binding EGF like growth factor(HBEGF) Related Genes Homo sapiens
GENERIF_SUMMARY Heparin-binding EGF-like growth factor decreases inducible nitric oxide synthase and nitric oxide production after intestinal ischemia/reperfusion injury., Site-directed mutagenesis of heparin-binding EGF-like growth factor (HB-EGF), HB-EGF mRNA and protein levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type., The current study reveals that HB-EGF mRNA is abundantly expressed in human and mouse adipose tissue, plasma HB-EGF levels increase in parallel with fat accumulation in human, and subjects with coronary artery disease have higher plasma HB-EGF levels., Bronchial epithelial compression regulates MAP kinase signaling and HB-EGF-like growth factor expression., Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells, nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF), Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF, data suggest that uterine receptivity may be regulated in part by the stromal-derived HB-EGF, HB-EGF cytoprotection is due, in part, to its ability to decrease reactive oxygen species production, Review. The mode of activation of EGFR in response to bacterial lipoteichoic acid involves cleavage of the transmembrane ligand HBEGF by ADAM 10., Transgenic expression of HB-EGF accelerates the proliferation of hepatocytes after partial hepatectomy, the effect of N- and C-terminal residues of the EGF-like domain of HB-EGF in the binding affinity to the EGF receptor on A431 cells, Diffusely expressed throughout normal and psoriatic epidermis and sparsely colocalized with EGFr in all viable epidermal layers, with increased colocalization in psoriatic epidermis., HB-EGF has an important role in the early pathogenesis of psoriasis., HB-EGF and FGF-2 act in concert to regulate the synthesis of elastin in injury/repair situations in pulmonary fibroblasts., proHB-EGF shedding induced by TPA and angiotensin II requires PACSIN3 as an upregulator, Heparin-binding EGF-like growth factor has a role in Angiopoietin-mediated recruitment of vascular smooth muscle cells., GnRH-induced transactivation of the EGF-R and the subsequent ERK1/2 phosphorylation result from ectodomain shedding of HBEGF., HB-EGF blocks cytokine-induced NF-kappaB activation and decreases nitric oxide production, interferes with cytokine-induced IkappaB kinase activity, inhibits phosphorylation and degradation of IkappaBalpha, and suppresses release of proinflammatory IL-8., Results suggest that epidermal growth factor receptor HER-mediated autocrine and paracrine signaling by heparin-binding EGF-like growth factor or other EGF family members induces cytotrophoblast differentiation to an invasive phenotype., Cis-acting element mediating gastrin responsiveness was mapped to the -69 to -58 region of the HB-EGF promoter. Gastrin stimulation was PKC dependent and at least partially mediated by activation of the EGF receptor., The spatial and temporal pattern of HB-EGF expression suggest that HB-EGF may an important local regulator of ovarian function and structure., relevance of a p38-ADAM-HB-EGF-EGFR-dependent pathway and its potential significance for tumor cells in evasion of chemotherapeutic agent-induced apoptosis, HB-EGF might be a more important tumor growth regulator of malignant fibrous histiocytoma through autocrine or paracrine pathways, when compared with betacellulin., HB-EGF is a potent inducer of tumor growth and angiogenesis, the heparin-binding domain serves as a negative regulator of heparin-binding EGF-like Growth Factor, Results indicate that pro-heparin-binding EGF-like growth factor (pro-HB-EGF) shedding and subsequent HB-EGF C terminal fragment signaling are related with progression of the cell cycle., ADAM12m is highly expressed in human glioblastomas and may play a role in the prominent proliferation of the glioblastomas through shedding of heparin-binding epidermal growth factor, HB-EGF has a function in endometrial maturation in mediating decidualization and attenuating TNF alpha- and TGF beta-induced apoptosis of endometrial stromal cells., HB-EGF/HER-1 signaling is relevant to mesenchymal stem cell biology, by regulating both proliferation and differentiation, These results suggested that HB-EGF in peritoneal fluid might play a key role in cell survival and in the proliferation of OVCA., HB-EGF may play a vital role in regulating luteal growth in a juxtacrine manner and through activating HER4 signalling, HB-EGF is one of the factors that are significantly upregulated in PVR (proliferative vitreoretinopathy) retinas., Recombinant HB-EGF decreases proinflammatory cytokine-stimulated NF-kappa B activation and nitric oxide production via activation of the phosphoinositide-3-kinase signaling pathway., A post-transcriptional mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling to inhibit apoptosis., HB-EGF and amphiregulin mediate retinoic-acid induced epidermal hyperplasia, results suggest a novel role for the cytoplasmic domain of HB-EGF that is regulated by phosphorylation, lysophosphatidic acid-induced IL-8 secretion is partly dependent on EGFR transactivation regulated by PKCdelta-dependent activation of Lyn kinase and MMPs and proHB-EGF, Inward potassium current in bladder urothelial cells(BUC) can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play role in pathophysiology of interstitial cystitis., Glutamatergic neurotransmission plays a crucial role in regulating ectodomain shedding of transgenic HB-EGF in the brains of transgenic mice that overexpress human HB-EGF., Nardilysin has an essential role in HB-EGF ectodomain shedding, which is regulated by the modulation of sheddase activity, Results demonstrate that mRNA stability and in particular the heparin binding epidermal growth factor like growth factor (HB-EGF) 3'-untranslated region is involved in HB-EGF mRNA induction., Chemotherapy-induced HB-EGF activation represents a critical mechanism of inducible chemotherapy resistance., HB-EGF carboxyl-terminal fragment is a potent regulator of gene expression via its interaction with the transcriptional repressor Bcl6., These findings demonstrate that amino-terminally truncated, membrane-bound form of HB-EGF stimulates cell proliferation but lacks insulin-like signalling., HB-EGF is up-regulated in tumor cells of SCC but not BCC of the skin. HB-EGF is also overexpressed in asymptomatic epidermis adjacent to both SCC and BCC, relative to normal skin., Gbetagamma mediates UVB-induced human keratinocyte apoptosis by augmenting the ectodomain shedding of HB-EGF, which sequentially activates EGFR and p38, activation of PPARdelta is a major event in psoriasis, contributing to the hyperproliferative phenotype by induction of HB-EGF., The maintenance of the activation level of EGFR, which determines the cellular invasive potential, operates through an autocrine loop involving the JNK-dependent production of uPA and HB-EGF activity., Plasma/bladder concentrations of recombinant human rhHB-EGF equivalents were significantly lower following the intravesicular route than following intravenous administration. Histologic tissue examination indicated no toxicity attributable to rhHB-EGF., HB-EGF regulated epithelial repair is enhanced by IL-13 from airway epithelial cells, Juxtacrine activation of EGFR by membrane-anchored HB-EGF may play an important role in the regulation of tight junction proteins and transepithelial resistance., alters the phenotype of keratinocytes in a manner similar to that observed during epidermal repair, TNFalpha may play a key role in cooperation with HB-EGF and AREG in the proliferation of epidermal keratinocytes at the psoriatic skin lesions., HBEGF was present in almost all breast cancers studied. High expression is related to the biological aggressiveness of breast cancer., HB-EGF acts as a negative adipogenesis regulator during the early but not later stages of adipocyte differentiation, block the commitment of pluripotent mesenchymal cells to the adipocyte lineage triggered by bone morphogenic protein 4., Review. HB-EGF is implicated in angiogenesis, wound healing, blastocyst implantation, atherosclerosis, & tumor formation. It is the diphtheria toxin receptor., A novel hairless model on an atopic dermatitis-prone genetic background generated by DTR transgenesis is reported., HBEGF-mediated signaling significantly reduces trophoblast cell death at term and its deficiency in preeclampsia could negatively impact trophoblast survival., These results suggest that HB-EGF-Cys/Ser(134/143) antagonizes EGFRs., The roles of HB-EGF in cell adhesion, invasion, and angiogenesis in ovarian cancer, were examined., HB-EGF regulates endothelial cell function via stimulation of eNOS and nitric oxide production to promote eNOS dependent angiogenesis., Pro-inflammatory stimuli induce the release of HB-EGF from mesenchyme cells, which stimulates DNA-replication in initiated/premalignant hepatocytes, At least three genes, orthologous to loci in this LD block, HBEGF, IK, and SRA1, result independently in a phenotype of myocardial contractile dysfunction when their expression is reduced with morpholino antisense reagents., Preclinical neonatal rat studies of heparin-binding EGF-like growth factor in protection of the intestines from necrotizing enterocolitis., Increased HB-EGF expression may be implicated in the pathogenesis and development of gastric carcinoma., HBEGF is a potent dilator of terminal mesenteric arterioles., These results demonstrate that HB-EGF-induced eNOS activation depends on p42/p44 MAPK, PI3K/Akt pathways and endogenous VEGF in HaCaT cells., lentivirus-mediated expression of soluble HB-EGF, but not soluble amphiregulin, strongly enhanced keratinocyte migration, even in the presence of metalloproteinase inhibitors, Measuring HIF1a, HB-EGF, and VEGF-C expression may contribute to a better understanding of the prognosis of patients with soft tissue sarcoma and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens., Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures., This data suggests that ethanol-induced apoptosis was reduced by HB-EGF, while hESC pluripotency was maintained., Increased serum HB-EGF is associated with heart hypertrophy and elevated blood cholesterol., We demonstrated that human adrenocortical carcinoma cells express HB-EGF, HBEGF advances trophoblast extravillous differentiation through coordinate activation of PI3 kinase, ERK, MAPK14, and JNK, while only MAPK14 is required for its antiapoptotic activity., reduction of antiphospholipid-mediated HB-EGF represents an mechanism that is responsible for the defective placentation and heparin protects from aPL-induced damage by inhibiting antibody binding, mAbs efficiently inhibited ectodomain shedding of proHB-EGF, and consequently prevented the cell growth of the EGFR-expressing cells in a co-culture system with proHB-EGF-expressing cells., induces several genes characteristics of columnar phenotypes of esophageal squamous epithelium in a paracrine manner, HB-EGF participate in transactivation of EGF receptor under oxidative stress., Endothelial-derived PDGFB and HBEGF both are required to control pericyte motility, proliferation, and recruitment along the endothelial cell tube ablumenal surface., Recombinant HB-EGF significantly promotes rat PC12 cell neurite outgrowth, an effect blocked by EGF receptor (EGFR) inhibition or mitogen-activated protein kinase (MAPK) inhibition, but not by tyrosine kinase inhibition., Expression of HB-EGF is regulated by miR-212 in head and neck squamous cell carcinoma., Results suggest that LTD induces EGF receptor transactivation through the release of HB-EGF in human bronchial epithelial cells with downstream release of CXCL8., MT1-MMP co-expressed with HB-EGF in ovarian carcinoma cells potentiates the activity of HB-EGF to promote invasive tumor growth and spreading in vivo., PKCalpha and PKCdelta regulate ADAM17-mediated ectodomain shedding of heparin binding-EGF through separate pathways., ATP induces HB-EGF synthesis and release by interacting with the P2 purinergic receptor and through p38 and ERK1/2 signaling in response to a challenging environment., brief exposure to HB-EGF, but not to EGF, is sufficient to induce prolonged activation of the EGF receptor and to enhance healing, Hypoxic induction of PAR-2 was found to elicit an angiogenic endothelial cell phenotype and to specifically up-regulate heparin-binding EGF-like growth factor (HB-EGF)., findings indicate that HB-EGF and PDGF reciprocally mediate the interaction of cancer cells with cancer-associated fibroblasts, promoting cancer cell proliferation in a paracrine manner, LIV-1 is involved in prostate cancer progression as an intracellular target of growth factor receptor signaling which promoted EMT and cancer metastasis, These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia., Heparin-binding epidermal growth factor-like growth factor is a potent autocrine regulator of invasion activity in oral squamous cell carcinoma., Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor., variant 1936T prevents hsa-miR-1207-5p from down-regulating HBEGF in podocytes, study is the first report demonstrating a role for the ADAM-HBEGF-EGF receptor axis in Ox-PAPC induction of IL-8 in HAECs., expression of HB-EGF in human KCs triggers a migratory and invasive phenotype with many features of epithelial-mesenchymal transition (EMT), which may be beneficial in the context of cutaneous wound healing., HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy., Results suggest that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a target for oral cancer and that CRM197 is effective in oral cancer therapy., results indicate that Abl kinases negatively regulate HNSCC invasive processes through suppression of an HB-EGF autocrine loop responsible for activating a EGFR-Src-cortactin cascade, Our results show that HB-EGF acts as a cell proliferation and cell survival factor in cancer cells., HB-EGF overexpression and Kras(G12D) together, but neither alone, increase cancer cell proliferation., Results suggest that HB-EGF plays a pivotal role in the acquisition of tumor aggressiveness in TNBC by orchestrating a molecular hierarchy regulating tumor angiogenesis., Hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling-dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor., Correlation has been found between HB-EGF expression/immunostaining and the different types of analyzed soft tissue sarcomas., visualized spatiotemporal regulation of proHB-EGF shedding in individual cells using a simple method that measures changes in fluorescence ratios, A reciprocal cross-talk between intrahepatic cholangiocarcinoma cells and myofibroblasts through the HB-EGF/EGFR axis contributes to CCA progression., The study suggest that one of the causes of unexplained miscarriages may result from the impaired expression of heparanase and heparin-binding EGF-like growth factor., HB-EGF acts as a potent paracrine and/or autocrine chemotactic factor as well as a mitogen that mediates HER1 and/or HER4 in the invasion and metastasis of thyroid carcinoma cells., Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo., Heparin-binding epidermal growth factor and CD9 are likely implicated in processes that are highly relevant for MS lesion formation, a mechanism of a probiotic-derived soluble protein in modulating intestinal epithelial cell homeostasis through ADAM17-mediated HB-EGF release, leading to transactivation of EGFR., studies suggest disintegrin and metalloproteinase domain-containing protein 12(ADAM 12S) and heparin-binding epidermal growth factor-like growth factor(HB-EGF) are involved in cellular plasticity resulting in production of brown adipose tissue-like cells, Knockdown of HSP27 by shRNA decreased HB-EGF plus CXCL5-mediated tumor spheroid formation in a three-dimensional culture system, suggesting that AKT/HSP27 was required for HB-EGF/CXCL5-mediated cancer progression, HB-EGF is a biomarker for LPA1 receptor activation in human breast and prostate cancers., the relative expression of hyalurosome (CD44, HAS3, HB-EGF) genes was found to be reduced in patients prior to topical treatment and to be notably increased following treatment., MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF., Suggest high levels of HB-EGF contribute to carotid plaque stabilization and reduce the incidence of acute coronary events., Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of overactive bladder syndrome treatment., Studies indicate that heparin-binding EGF-like growth factor (HB-EGF) is a therapeutic target in some types of cancers., Data suggest that placental expression of HBEGF, EGF (epidermal GF), and TGFA (transforming GF alpha) is down-regulated in pre-eclampsia as compared to normal term birth; each growth factor blocks cell death/apoptosis of cytotrophoblast cell line., Serum sHB-EGF is closely correlated with advanced stage gastric cancer and can be a promising serological biomarker for GC.,
OMIM_DISEASE Diphtheria, susceptibility to,
SP_COMMENT function:May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts and smooth muscle but not endothelial cells. It is able to bind EGF receptors with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor., PTM:O-linked glycan attachment sites were determined by Edman degradation, O-glycanase digest suggests mucin-type glycosylation (done in HB-EGF purified from histiocytic lymphoma cell line U-937)., PTM:Several N-termini have been identified by direct sequencing. The forms with N-termini 63, 73 and 74 have been tested and found to be biologically active., similarity:Contains 1 EGF-like domain., subcellular location:Mature HB-EGF is released into the extracellular space and probably binds to a receptor.,