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Gene Review

Hbegf  -  heparin-binding EGF-like growth factor

Rattus norvegicus

Synonyms: Dtr, GFHB, Hb-egf, Hegfl, Proheparin-binding EGF-like growth factor
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Disease relevance of Hbegf


High impact information on Hbegf


Chemical compound and disease context of Hbegf


Biological context of Hbegf


Anatomical context of Hbegf


Associations of Hbegf with chemical compounds

  • Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively [10].
  • Both p42 MAPK activation and HB-EGF mRNA induction were inhibited by genistein, indicating a requirement for an upstream tyrosine kinase activity [12].
  • HB-EGF inhibited the swelling of glial cells in retinal slices, via stimulation of the synaptic release of glutamate and subsequent activation of glial metabotropic glutamate receptors which resulted in an autocrine release of purinergic receptor agonists [2].
  • To investigate signaling molecules involved in HB-EGF-induced DNA synthesis, we pretreated VSMC with the specific ERK kinase mitogen-activated kinase (MEK) inhibitor PD98059 and the phosphatidylinositol 3-kinase inhibitor LY294002 [13].
  • The kainate-induced elevation of [Ca2+]i in hippocampal neurons was not altered in cultures pretreated with HB-EGF, suggesting an excitoprotective mechanism different from that of previously characterized excitoprotective growth factors [7].

Physical interactions of Hbegf

  • Matrix metalloproteinase (MMP)-dependent shedding of heparin-binding epidermal growth factor (HB-EGF) and subsequent activation of the EGF receptor (EGFR) in the cardiovasculature is emerging as a unique mechanism signaling growth effects of diverse G protein-coupled receptors (GPCRs) [14].

Regulatory relationships of Hbegf

  • EC-SOD also inhibited the induction of HB-EGF by 12-O-tetradecanoylphorbol-13-acetate (TPA) in RASMC by 60% [10].
  • PD98059 inhibited HB-EGF-induced ERK activation, whereas it had no effect on Akt activation by HB-EGF [13].
  • Ang II also upregulated vascular endothelial growth factor (VEGF) expression in an HB-EGF/EGFR-dependent manner [15].
  • Conversely, pretreatment with an intracellular Ca2+ antagonist or an antioxidant blocked AngII-induced HB-EGF shedding [16].
  • Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is one of five well-described growth factors which bind to and activate the EGF receptor [17].

Other interactions of Hbegf

  • However, the expression of neither EGF nor HB-EGF was changed after obstruction [18].
  • ERK phosphorylation was attenuated by 1) neutralizing EGFR antibodies and the EGFR kinase inhibitor, AG1478, 2) neutralizing HB-EGF, but not amphiregulin, antibodies, heparin, or CM197, and 3) pharmacological inhibitors of matrix-degrading metalloproteinases or TACE small interfering RNA [9].
  • The survival promoting effect of HB-EGF is mediated via astroglial cells and utilizes the MAPK as well as the Akt-signaling pathway [19].
  • In conclusion, this study demonstrates that gastrin enhances gastric mucosal integrity through COX-2, which is partially mediated by HB-EGF, and PGE(2) upregulation in rats [20].
  • Thus, Ang II is involved in the VEGF-Ang-Tie2 system via HB-EGF-mediated EGFR transactivation, and this link should be considerable in pathological conditions in which collateral blood flow is required [15].

Analytical, diagnostic and therapeutic context of Hbegf


  1. Tissue distribution and plasma clearance of heparin-binding EGF-like growth factor (HB-EGF) in adult and newborn rats. Feng, J., Mehta, V.B., El-Assal, O.N., Wu, D., Besner, G.E. Peptides (2006) [Pubmed]
  2. HB-EGF: increase in the ischemic rat retina and inhibition of osmotic glial cell swelling. Weuste, M., Wurm, A., Iandiev, I., Wiedemann, P., Reichenbach, A., Bringmann, A. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  3. A role of heparin-binding epidermal growth factor-like growth factor in cardiac remodeling after myocardial infarction. Tanaka, N., Masamura, K., Yoshida, M., Kato, M., Kawai, Y., Miyamori, I. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  4. Upregulation of endogenous heparin-binding EGF-like growth factor (HB-EGF) expression after intestinal ischemia/reperfusion injury. Xia, G., Rachfal, A.W., Martin, A.E., Besner, G.E. Journal of investigative surgery : the official journal of the Academy of Surgical Research. (2003) [Pubmed]
  5. Heparin-binding EGF-like growth factor contributes to reduced glomerular filtration rate during glomerulonephritis in rats. Feng, L., Garcia, G.E., Yang, Y., Xia, Y., Gabbai, F.B., Peterson, O.W., Abraham, J.A., Blantz, R.C., Wilson, C.B. J. Clin. Invest. (2000) [Pubmed]
  6. Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules. Sakai, M., Zhang, M., Homma, T., Garrick, B., Abraham, J.A., McKanna, J.A., Harris, R.C. J. Clin. Invest. (1997) [Pubmed]
  7. Heparin-binding epidermal growth factor-like growth factor in hippocampus: modulation of expression by seizures and anti-excitotoxic action. Opanashuk, L.A., Mark, R.J., Porter, J., Damm, D., Mattson, M.P., Seroogy, K.B. J. Neurosci. (1999) [Pubmed]
  8. Increased expression of heparin binding epidermal growth-factor-like growth factor mRNA in the kidney of streptozotocin-induced diabetic rats. Lee, Y.J., Shin, S.J., Lin, S.R., Tan, M.S., Tsai, J.H. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  9. 5-HT2A receptor induces ERK phosphorylation and proliferation through ADAM-17 tumor necrosis factor-alpha-converting enzyme (TACE) activation and heparin-bound epidermal growth factor-like growth factor (HB-EGF) shedding in mesangial cells. Göoz, M., Göoz, P., Luttrell, L.M., Raymond, J.R. J. Biol. Chem. (2006) [Pubmed]
  10. Inhibition of gene expression of heparin-binding epidermal growth factor-like growth factor by extracellular superoxide dismutase in rat aortic smooth muscle cells. Nishimura, M., Ookawara, T., Eguchi, H., Fujiwara, N., Yoshihara, D., Yasuda, J., Mimura, O., Suzuki, K. Free Radic. Res. (2006) [Pubmed]
  11. An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF-like growth factor ectodomain shedding. Kim, J., Lin, J., Adam, R.M., Lamb, C., Shively, S.B., Freeman, M.R. J. Cell. Biochem. (2005) [Pubmed]
  12. Heparin-binding epidermal-growth-factor-like growth factor gene expression is induced by scrape-wounding epithelial cell monolayers: involvement of mitogen-activated protein kinase cascades. Ellis, P.D., Hadfield, K.M., Pascall, J.C., Brown, K.D. Biochem. J. (2001) [Pubmed]
  13. Signaling mechanisms of heparin-binding epidermal growth factor-like growth factor in vascular smooth muscle cells. Reynolds, C.M., Eguchi, S., Frank, G.D., Motley, E.D. Hypertension (2002) [Pubmed]
  14. Agonist-induced activation of matrix metalloproteinase-7 promotes vasoconstriction through the epidermal growth factor-receptor pathway. Hao, L., Du, M., Lopez-Campistrous, A., Fernandez-Patron, C. Circ. Res. (2004) [Pubmed]
  15. Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation. Fujiyama, S., Matsubara, H., Nozawa, Y., Maruyama, K., Mori, Y., Tsutsumi, Y., Masaki, H., Uchiyama, Y., Koyama, Y., Nose, A., Iba, O., Tateishi, E., Ogata, N., Jyo, N., Higashiyama, S., Iwasaka, T. Circ. Res. (2001) [Pubmed]
  16. G protein coupling and second messenger generation are indispensable for metalloprotease-dependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor. Mifune, M., Ohtsu, H., Suzuki, H., Nakashima, H., Brailoiu, E., Dun, N.J., Frank, G.D., Inagami, T., Higashiyama, S., Thomas, W.G., Eckhart, A.D., Dempsey, P.J., Eguchi, S. J. Biol. Chem. (2005) [Pubmed]
  17. Heparin-binding epidermal growth factor-like growth factor, an immediate-early gene for mesangial cells, is up-regulated in the Thy-1.1 model. Polihronis, M., Murphy, B.F., Pearse, M.J., Power, D.A. Exp. Nephrol. (1996) [Pubmed]
  18. Increased TGF-alpha and EGF Receptor mRNA Expression in Response to Neonatal Unilateral Partial Ureter Obstruction in Rats. Bor, M.V., Shi, Y., Sorensen, B.S., Wen, J.G., Frokiaer, J., Djurhuus, J.C., Nexo, E. Nephron Exp. Nephrol. (2006) [Pubmed]
  19. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) regulates survival of midbrain dopaminergic neurons. Farkas, L.M., Krieglstein, K. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  20. Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats. Komori, M., Tsuji, S., Sun, W.H., Tsujii, M., Kawai, N., Yasumaru, M., Kakiuchi, Y., Kimura, A., Sasaki, Y., Higashiyama, S., Kawano, S., Hori, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  21. Heparin-binding epidermal growth factor-like growth factor regulates fibroblast growth factor-2 expression in aortic smooth muscle cells. Peifley, K.A., Alberts, G.F., Hsu, D.K., Feng, S.L., Winkles, J.A. Circ. Res. (1996) [Pubmed]
  22. Role of heparin-binding epidermal growth factor-like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy. Kiso, S., Kawata, S., Tamura, S., Higashiyama, S., Ito, N., Tsushima, H., Taniguchi, N., Matsuzawa, Y. Hepatology (1995) [Pubmed]
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