Heregulin enhances regenerative proliferation in postnatal rat utricular sensory epithelium after ototoxic damage.

摘要: Hair cell loss due to acoustic and ototoxic damage often leads hearing balance impairments. Although a spontaneous event in chicks lower vertebrates, hair replacement occurs at much frequency mammals presumably very low rate of supporting proliferation following injury. We report here that heregulin, member the neuregulin family, dramatically enhances cells postnatal rat utricular epithelial sheet cultures after gentamicin treatment, as revealed by bromo-deoxyuridine (BrdU) immunocytochemistry. A dose-dependent study shows maximal effects heregulin are achieved 3 nM. The mitogenic confirmed whole mount cultures. Autoradiography also number tritiated thymidine-labeled within layer. TaqMan quantitative RT-PCR analysis immunocytochemistry reveal its binding receptors (ErbB-2, ErbB-3 ErbB-4) expressed inner ear sensory epithelium. Of several ligands activating various ErbB receptors, including neuregulin-3, β-cellulin, heparin binding-epidermal growth factor (HB-EGF), transforming factor-α (TGF-α) EGF, most potent on cells. Because neuregulin-3 signals only through ErbB-4 does not show an effect, these data suggest activation ErbB-2-ErbB-3 heterodimeric complexes, rather than ErbB-4, is critical for proliferative response In addition, treatment induces upregulation mRNA. Considered together, may play important role regeneration damage.