title: [The role of HB-EGF in angiotensin II--signaling].
abstract: G-protein coupled receptor agonists such as phenylephrine, angiotensin II, and endothelin-1 are well-known inducers of cardiac hypertrophy. We demonstrated that both metalloproteinase inhibitor and HB-EGF neutralizing antibody abrogated the trans-activation of the receptor for epidermal growth factor by phenylephrine, angiotensin II, or endothelin-1 in cultured rat neonatal cardiomyocytes. We cloned ADAM12(a disintegrin and metalloprotease 12) as a specific enzyme to cleave HB-EGF in cardiomyocytes. We also showed that a metalloproteinase inhibitor attenuates cardiac hypertrophy in aortic banding mice. These data suggest that release of HB-EGF by ADAM12 plays a crucial role in hypertrophic signaling of cardiomyocytes, and that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine.
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D004815:Epidermal Growth Factor / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D000804:Angiotensin II; D004815:Epidermal Growth Factor